Professor James Leiper
- Honorary Professor (School of Cardiovascular & Metabolic Health)
email:
James.Leiper@glasgow.ac.uk
Institute of Cardiovascular and Medical Sciences, University of Glasgow, BHF Glasgow Cardiovascular Research Centre, 126 University Place
Biography
James Leiper is Professor of Molecular Medicine in the School of Cardiovascular and Metabolic Health. Originally trained in molecular biology at the MRC Clinical Research Centre, James became interested in cardiovascular physiology whilst working with Professor Patrick Vallance in the Centre for Clinical Pharmacology at UCL and continued this work after taking up a position as Programme Leader at the MRC Laboratory for Medical Sciences. In 2017 James group was recruited to SCMH at the University of Glasgow where their research focus will be the translation of findings from basic science to human health and disease.
Research Grants:
1) MRC Intramural Research Programme Funding (2015-2020) Leiper J*. £2,800,000. (terminated Sept 2017 on departure from MRC London institute of Medical Sciences)
2) British Heart Foundation Translational Grant. Development of selective inhibitors of DDAH1 for use in man. Leiper J* and Lambden S. (2015-2016) £98,000.
3) The Chelsea and Westminster Health Trust PhD Studentship. The role of endogenous inhibitors of nitric oxide synthesis in vasculardysfunction associated with pre-eclampsia. Johnson M and Leiper J. (2014-2017) £102,000.
4) British Heart Foundation Project Grant. The role of nitric oxide signalling in the neurovascular unit. Scott J, Leiper J and Eddison P. (2014-2017) £299,654.
5) British Heart Foundation ICTEM 4 year PhD training scheme. Harding, S. (2013-2021) £2,571,706♯. Leiper as co-applicant currently awarded 3 MRes/PhD studentships (approximate value £482,118).
6) British Heart Foundation Project Grant. Investigating the role of PKCε in vascular inflammation. Mason J, Randi, A, Leiper J and Haskard D. (2013-2016) £254,000.
7) British Heart Foundation PhD Studentship. The role of the DDAH/ADMA/NOS pathway in cardiac stem cell differentiation. (2012-2015) Leiper J*. £75,300.
8) MRC/BRC Chain Florey Fellowships to Tomlinson (Clinical Lecturer) and Lota (Clinical PhD) Investigating the role of ADMA/DDAH in chronic renal and pulmonary disease. (2010-2016). Leiper J*. £471,000.
9) MRC Technology Development Gap Fund. Dimethylarginine dimethylaminohydrolase 2 inhibition in Rheumatoid Arthritis (2012-2013) Leiper J*. £108,000.
10) MRC Intramural Research Programme Funding (2009-2015) Leiper J*. £2,800,000.
11) British Heart Foundation Project Grant. (2009-2012) Wojciak-Stothard B Wilkins M and Leiper J. The role of ADMA in the regulation of pulmonary endothelial cell-to-cell communication and endothelial permeability. £183,010.
12) British Heart Foundation Project Grant (2009-2012) Nandi M and Leiper J. The role of GTP cyclohydrolase feedback regulatory protein in the regulation of tetrahydrobiopterin synthesis in vivo. £254,086.
13) Wellcome Trust Seeding Drug Discovery Initiative (2008-2011) Leiper J*, Caddick S, McDonald N and Singer M. Dimethylarginine dimethylaminohydrolase 1 Inhibition in Sepsis £4,200,000
14) ESRC Platform Grant (2006-2011) Caddick S, Partridge L, McDonald N Leiper J. Methylarginine processing enzymes. £760,000.
15) British Heart Foundation Programme Grant (2005-2011) Vallance P, Leiper J*, Hingorani A. ADMA and DDAH signalling in vascular disease. £1,302,907.
16) Wellcome Trust Project Grant (2005-2008) Mohammed-Ali V, Vallance P, Leiper J, Speakman J. Investigation of the regulation of adipose ADMA production. £236,395.
17) European Commission FP6 (2005-2009) The Pulmotension Consortium. €11,000,000. UCL allocation £285,000 (James Leiper P.I. at UCL).
18) European Commission FP6 Network of Excellence (2004-2008) The European Vascular Genomics Consortium. €9,000,000. UCL allocation £120,000 (James Leiper P.I. at UCL).
Research interests
Work in my laboratory is focussed on understanding the mechanisms that regulate nitric oxide (NO) signalling in health and disease. NO is a signalling molecule with protean functions in the cardiovascular, immune and central nervous systems. In the cardiovascular system dysregulated nitric oxide synthesis results in loss of cardiovascular homeostasis and contributes to a range of diseases including hypertension, atherosclerosis the cardiovascular collapse seen in septic shock. Therapeutic approaches to directly target NO have had limited success and therefore we have focussed on endogenous regulatory pathways that might facilitate therapeutically appropriate regulation of NO production. In particular we have focussed on understanding how endogenously produced inhibitors of NO synthesis might be harnessed therapeutically. To facilitate translation of our understanding of nitric oxide signalling for health care benefit we recently established a new biotech company backed by venture capital funding to perform clinical trials of new drugs for the treatment of septic shock.
Research groups
Publications
2024
Hanson Ng, Y. Y. et al. (2024) Asymmetric dimethylarginine enables depolarizing spikes and vasospasm in mesenteric and coronary resistance arteries. Hypertension, 81(4), pp. 764-775. (doi: 10.1161/HYPERTENSIONAHA.123.22454) (PMID:38226470) (PMCID:PMC10956675)
2023
Sri, S. et al. (2023) A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia. Cerebral Circulation - Cognition and Behavior, 5, 100189. (doi: 10.1016/j.cccb.2023.100189) (PMID:37941765) (PMCID:PMC10628644)
Dowsett, L. , Duluc, L., Higgins, E., Alghamdi, F., Fast, W., Salt, I. P. and Leiper, J. (2023) Asymmetric dimethylarginine positively modulates calcium-sensing receptor signalling to promote lipid accumulation. Cellular Signalling, 107, 110676. (doi: 10.1016/j.cellsig.2023.110676) (PMID:37028778)
2021
Boder, P., Mary, S. , Mark, P. B. , Leiper, J. , Dominiczak, A. F. , Padmanabhan, S. , Rampold, L. and Delles, C. (2021) Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension. Journal of Hypertension, 39(8), pp. 1490-1504. (doi: 10.1097/HJH.0000000000002861) (PMID:34187999) (PMCID:PMC7611110)
2020
Dowsett, L. , Higgins, E., Alanazi, S., Alshuwayer, N. A., Leiper, F. C. and Leiper, J. (2020) ADMA: A key player in the relationship between vascular dysfunction and inflammation in atherosclerosis. Journal of Clinical Medicine, 9(9), 3026. (doi: 10.3390/jcm9093026) (PMID:32962225) (PMCID:PMC7563400)
2019
Zöllner, J., Lambden, S., Nasri, N. M., Leiper, J. and Johnson, M. R. (2019) Rapid onset of severe septic shock in the pregnant mouse. Biology of Reproduction, 100(2), pp. 505-513. (doi: 10.1093/biolre/ioy193) (PMID:30184059)
Leiper, J. (2019) Nitric oxide. In: Touyz, R. M. and Delles, C. (eds.) Textbook of Vascular Medicine. Springer: Cham, pp. 117-126. ISBN 9783030164805 (doi: 10.1007/978-3-030-16481-2_11)
2018
Lambden, S., Tomlinson, J., Piper, S., Gordon, A. C. and Leiper, J. (2018) Evidence for a protective role for the rs805305 single nucleotide polymorphism of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in septic shock through the regulation of DDAH activity. Critical Care, 22(1), 336. (doi: 10.1186/s13054-018-2277-5) (PMID:30538005) (PMCID:PMC6288902)
Bell, T., Araujo, M., Luo, Z., Tomlinson, J., Leiper, J. , Welch, W. J. and Wilcox, C. S. (2018) Regulation of fluid reabsorption in rat or mouse proximal renal tubules by asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase 1. American Journal of Physiology: Renal Physiology, 315(1), F74-F78. (doi: 10.1152/ajprenal.00560.2017) (PMID:29513072) (PMCID:PMC6087787)
Wang, C., Luo, Z., Carter, G., Wellstein, A., Jose, P. A., Tomlinson, J., Leiper, J. , Welch, W. J., Wilcox, C. S. and Wang, D. (2018) NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 314(3), R399-R406. (doi: 10.1152/ajpregu.00122.2017) (PMID:29167164)
Paul, E. J., Kalk, E., Tossell, K., Irvine, E. E., Franks, N. P., Wisden, W., Withers, D. J., Leiper, J. and Ungless, M. A. (2018) nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta. eNeuro, 5(5), ENEURO.0381-18.2018. (doi: 10.1523/ENEURO.0381-18.2018) (PMID:30456293) (PMCID:PMC6240015)
2017
Tesfai, A. et al. (2017) Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways. PLoS ONE, 12(8), e0183025. (doi: 10.1371/journal.pone.0183025) (PMID:28813479) (PMCID:PMC5557592)
Zöllner, J., Howe, L. G., Edey, L. F., O’Dea, K. P., Takata, M., Gordon, F., Leiper, J. and Johnson, M. R. (2017) The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice. Biology of Reproduction, 97(2), pp. 258-272. (doi: 10.1093/biolre/iox076) (PMID:29044422)
2016
Rodionov, R. N. et al. (2016) A novel pathway for metabolism of the cardiovascular risk factor homoarginine by alanine:glyoxylate aminotransferase 2. Scientific Reports, 6, 35277. (doi: 10.1038/srep35277) (PMID:27752063) (PMCID:PMC5082758)
Lange, C. et al. (2016) Dimethylarginine dimethylaminohydrolase-2 deficiency promotes vascular regeneration and attenuates pathological angiogenesis. Experimental Eye Research, 147, pp. 148-155. (doi: 10.1016/j.exer.2016.05.007) (PMID:27181226) (PMCID:PMC4912010)
Lambden, S., Martin, D., Vanezis, K., Lee, B., Tomlinson, J., Piper, S., Boruc, O., Mythen, M. and Leiper, J. (2016) Hypoxia causes increased monocyte nitric oxide synthesis which is mediated by changes in dimethylarginine dimethylaminohydrolase 2 expression in animal and human models of normobaric hypoxia. Nitric Oxide, 58, pp. 59-66. (doi: 10.1016/j.niox.2016.06.003) (PMID:27319282)
2015
Tomlinson, J. A.P. et al. (2015) Reduced renal methylarginine metabolism protects against progressive kidney damage. Journal of the American Society of Nephrology, 26(12), pp. 3045-3059. (doi: 10.1681/ASN.2014030280) (PMID:25855779) (PMCID:PMC4657823)
DʼMello, R., Sand, C. A., Pezet, S., Leiper, J. M. , Gaurilcikaite, E., McMahon, S. B., Dickenson, A. H. and Nandi, M. (2015) Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity. Pain, 156(10), pp. 2052-2060. (doi: 10.1097/j.pain.0000000000000269) (PMID:2609843) (PMCID:PMC4770343)
Dowsett, L. et al. (2015) Endothelial dimethylarginine dimethylaminohydrolase 1 is an important regulator of angiogenesis but does not regulate vascular reactivity or hemodynamic homeostasis. Circulation, 131(25), pp. 2217-2225. (doi: 10.1161/CIRCULATIONAHA.114.015064) (PMID:25910799)
Lambden, S. et al. (2015) Dimethylarginine dimethylaminohydrolase 2 regulates nitric oxide synthesis and hemodynamics and determines outcome in polymicrobial sepsis. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(6), pp. 1382-1392. (doi: 10.1161/ATVBAHA.115.305278) (PMID:25857313)
Ahmetaj-Shala, B. et al. (2015) Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs. Circulation, 131(7), pp. 633-642. (doi: 10.1161/CIRCULATIONAHA.114.011591) (PMID:25492024) (PMCID:PMC4768634)
2014
Starr, A., Sand, C. A., Heikal, L., Kelly, P. D., Spina, D., Crabtree, M., Channon, K. M., Leiper, J. M. and Nandi, M. (2014) Overexpression of GTP cyclohydrolase 1 feedback regulatory protein is protective in a murine model of septic shock. Shock, 42(5), pp. 432-439. (doi: 10.1097/SHK.0000000000000235) (PMID:25046538) (PMCID:PMC4851220)
Libri, V. et al. (2014) Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study. Lancet, 384(9942), pp. 504-513. (doi: 10.1016/S0140-6736(14)60382-2) (PMID:24794816)
Iannone, L., Zhao, L., Dubois, O., Duluc, L., Rhodes, C. J., Wharton, J., Wilkins, M. R., Leiper, J. and Wojciak-Stothard, B. (2014) miR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia. Biochemical Journal, 462(1), pp. 103-112. (doi: 10.1042/BJ20140486) (PMID:24895913)
Wang, Z. et al. (2014) Pharmacological inhibition of DDAH1 improves survival, haemodynamics and organ function in experimental septic shock. Biochemical Journal, 460(2), pp. 309-316. (doi: 10.1042/BJ20131666) (PMID:24611830)
Ghebremariam, Y. T., LePendu, P., Lee, J. C., Erlanson, D. A., Slaviero, A., Shah, N. H., Leiper, J. M. and Cooke, J. P. (2014) Response to letters regarding article, "Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine". Circulation, 129(13), e428-e428. (doi: 10.1161/CIRCULATIONAHA.114.009343) (PMID:24687654) (PMCID:PMC4105215)
2013
Tsang, H. et al. (2013) Role of asymmetric methylarginine and connexin 43 in the regulation of pulmonary endothelial function. Pulmonary Circulation, 3(3), pp. 675-691. (doi: 10.1086/674440) (PMID:24618552) (PMCID:PMC4070793)
Ghebremariam, Y. T., LePendu, P., Lee, J. C., Erlanson, D. A., Slaviero, A., Shah, N. H., Leiper, J. and Cooke, J. P. (2013) Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation, 128(8), pp. 845-853. (doi: 10.1161/CIRCULATIONAHA.113.003602) (PMID:23825361) (PMCID:PMC3838201)
2012
Caplin, B., Wang, Z., Slaviero, A., Tomlinson, J., Dowsett, L. , Delahaye, M., Salama, A., Wheeler, D. C. and Leiper, J. (2012) Alanine-glyoxylate aminotransferase-2 metabolizes endogenous methylarginines, regulates NO, and controls blood pressure. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(12), pp. 2892-2900. (doi: 10.1161/ATVBAHA.112.254078) (PMID:23023372)
Nandi, M., Kelly, P., Torondel, B., Wang, Z., Starr, A., Ma, Y., Cunningham, P., Stidwill, R. and Leiper, J. (2012) Genetic and pharmacological inhibition of dimethylarginine dimethylaminohydrolase 1 is protective in endotoxic shock. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(11), pp. 2589-97. (doi: 10.1161/ATVBAHA.112.300232) (PMID:22995517)
Caplin, B. and Leiper, J. (2012) Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators? Arteriosclerosis, Thrombosis, and Vascular Biology, 32(6), pp. 1343-1353. (doi: 10.1161/ATVBAHA.112.247726) (PMID:22460557) (PMCID:PMC3975829)
Woods, A., Leiper, J. M. and Carling, D. (2012) The role of ATM in response to metformin treatment and activation of AMPK [Letter]. Nature Genetics, 44(4), pp. 360-361. (doi: 10.1038/ng.2235) (PMID:22456733)
2011
Boult, J. K.R., Walker-Samuel, S., Jamin, Y., Leiper, J. M. , Whitley, G. S. J. and Robinson, S. P. (2011) Active site mutant dimethylarginine dimethylaminohydrolase 1 expression confers an intermediate tumour phenotype in C6 gliomas. Journal of Pathology, 225(3), pp. 344-352. (doi: 10.1002/path.2904) (PMID:21590769)
Leiper, J. and Nandi, M. (2011) The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nature Reviews Drug Discovery, 10(4), pp. 277-291. (doi: 10.1038/nrd3358) (PMID:21455237)
Pullamsetti, S. S. et al. (2011) cAMP phosphodiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases. Circulation, 123(11), pp. 1194-204. (doi: 10.1161/CIRCULATIONAHA.110.941484) (PMID:21382892)
Pullamsetti, S. S. et al. (2011) The role of dimethylarginine dimethylaminohydrolase in idiopathic pulmonary fibrosis. Science Translational Medicine, 3(87), 87ra53. (doi: 10.1126/scitranslmed.3001725) (PMID:21677199)
Lakhani, K., Kay, A. R., Leiper, J. , Barry, J. A. and Hardiman, P. J. (2011) Symmetric dimethylarginine (SDMA) is raised in women with polycystic ovary syndrome: A pilot study. Journal of Obstetrics and Gynaecology, 31(5), pp. 417-419. (doi: 10.3109/01443615.2011.569779) (PMID:21627426)
2010
Gray, G. A., Patrizio, M., Sherry, L., Miller, A. A. , Malaki, M., Wallace, A. F., Leiper, J. M. and Vallance, P. (2010) Immunolocalisation and activity of DDAH I and II in the heart and modification post-myocardial infarctioN. Acta Histochemica, 112(5), pp. 413-423. (doi: 10.1016/j.acthis.2009.02.009) (PMID:19481782)
Torondel, B., Nandi, M., Kelly, P., Wojciak-Stothard, B., Fleming, I. and Leiper, J. (2010) Adenoviral-mediated overexpression of DDAH improves vascular tone regulation. Vascular Medicine, 15(3), pp. 205-213. (doi: 10.1177/1358863X09360264) (PMID:20219849)
Caplin, B. et al. (2010) Circulating methylarginine levels and the decline in renal function in patients with chronic kidney disease are modulated by DDAH1 polymorphisms. Kidney International, 77(5), pp. 459-467. (doi: 10.1038/ki.2009.463) (PMID:20010544)
Ivashchenko, C. Y., Bradley, B. T., Ao, Z., Leiper, J. , Vallance, P. and Johns, D. J. (2010) Regulation of the ADMA-DDAH system in endothelial cells: a novel mechanism for the sterol response element binding proteins, SREBP1c and -2. American Journal of Physiology: Heart and Circulatory Physiology, 298(1), H251-H258. (doi: 10.1152/ajpheart.00195.2009) (PMID:19915177) (PMCID:PMC2806130)
Arrigoni, F., Ahmetaj, B. and Leiper, J. (2010) The Biology and therapeutic potential of the DDAH/ADMA pathway. Current Pharmaceutical Design, 16(37), pp. 4089-4102. (doi: 10.2174/138161210794519246) (PMID:21247398)
Breckenridge, R. A., Kelly, P., Nandi, M., Vallance, P. J., Ohun, T. J. and Leiper, J. (2010) A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development. International Journal of Developmental Biology, 54(1), pp. 215-226. (doi: 10.1387/ijdb.072356rb) (PMID:19757398)
2009
Fiedler, L. R., Bachetti, T., Leiper, J. , Zachary, I., Chen, L., Renné, T. and Wojciak-Stothard, B. (2009) The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(12), pp. 2117-2124. (doi: 10.1161/ATVBAHA.109.194035) (PMID:19778944)
Wojciak-Stothard, B., Torondel, B., Zhao, L., Renne, T. and Leiper, J. M. (2009) Modulation of Rac1 activity by ADMA/DDAH regulates pulmonary endothelial barrier function. Molecular Biology of the Cell, 20(1), pp. 33-42. (doi: 10.1091/mbc.E08-04-0395) (PMID:18923147) (PMCID:PMC2613095)
2008
Nandi, M., Kelly, P., Vallance, P. and Leiper, J. (2008) Over-expression of GTP-cyclohydrolase 1 feedback regulatory protein attenuates LPS and cytokine-stimulated nitric oxide production. Vascular Medicine, 13(1), pp. 29-36. (doi: 10.1177/1358863X07085916)
Onozato, M. L., Tojo, A., Leiper, J. , Fujita, T., Palm, F. and Wilcox, C. S. (2008) Expression of NG,NG-dimethylarginine dimethylaminohydrolase and protein arginine N-methyltransferase isoforms in diabetic rat kidney: effects of angiotensin II receptor blockers. Diabetes, 57(1), pp. 172-180. (doi: 10.2337/db06-1772) (PMID:17909098)
Wojciak‐Stothard, B. and Leiper, J. (2008) Rho GTPases and hypoxia in pulmonary vascular endothelial cells. Methods in Enzymology, 439, pp. 267-283. (doi: 10.1016/S0076-6879(07)00420-X) (PMID:18374171)
2007
Wang, D. et al. (2007) Isoform-specific regulation by N(G),N(G)-dimethylarginine dimethylaminohydrolase of rat serum asymmetric dimethylarginine and vascular endothelium-derived relaxing factor/NO. Circulation Research, 101(6), pp. 627-35. (doi: 10.1161/CIRCRESAHA.107.158915) (PMID:17673667)
Hartzoulakis, B. et al. (2007) Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis. Bioorganic and Medicinal Chemistry Letters, 17(14), pp. 3953-3956. (doi: 10.1016/j.bmcl.2007.04.095) (PMID:17543521)
Wojciak-Stothard, B., Torondel, B., Tsang, L. Y. F., Fleming, I., Fisslthaler, B., Leiper, J. M. and Vallance, P. (2007) The ADMA/DDAH pathway is a critical regulator of endothelial cell motility. Journal of Cell Science, 120(6), pp. 929-942. (doi: 10.1242/jcs.002212) (PMID:17327280)
Leiper, J. et al. (2007) Disruption of methylarginine metabolism impairs vascular homeostasis. Nature Medicine, 13(2), pp. 198-203. (doi: 10.1038/nm1543) (PMID:17273169)
Bulau, P., Zakrzewicz, D., Kitowska, K., Leiper, J. , Gunther, A., Grimminger, F. and Eickelberg, O. (2007) Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA. American Journal of Physiology: Lung Cellular and Molecular Physiology, 292(1), L18-L24. (doi: 10.1152/ajplung.00076.2006) (PMID:16891395)
Mookerjee, R. P. et al. (2007) Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis. Hepatology, 45(1), pp. 62-71. (doi: 10.1002/hep.21491) (PMID:17187433)
2006
Leiper, J. and Vallance, P. (2006) New tricks from an old dog: nitric oxide-independent effects of dimethylarginine dimethylaminohydrolase. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(7), pp. 1419-1420. (doi: 10.1161/01.ATV.0000229598.55602.17) (PMID:16794231)
Nandi, M., Leiper, J. , Arrigoni, F., Hislop, A., Vallance, P. and Haworth, S. (2006) Developmental regulation of GTP-CH1 in the porcine lung and its relationship to pulmonary vascular relaxation. Pediatric Research, 59(6), pp. 767-772. (doi: 10.1203/01.pdr.0000219301.19958.a0) (PMID:16641207)
2005
Leiper, J. M. (2005) The DDAH-ADMA-NOS pathway. Therapeutic Drug Monitoring, 27(6), pp. 744-746. (doi: 10.1097/01.ftd.0000179849.42395.11) (PMID:16404814)
Smith, C. L., Anthony, S., Hubank, M., Leiper, J. M. and Vallance, P. (2005) Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA. PLoS Medicine, 2(10), e264. (doi: 10.1371/journal.pmed.0020264) (PMID:16190779) (PMCID:PMC1240048)
Vallance, P. and Leiper, J. (2005) Asymmetric dimethylarginine and kidney disease: marker or mediator? Journal of the American Society of Nephrology, 16(8), pp. 2254-2256. (doi: 10.1681/ASN.2005050539) (PMID:15987745)
Rossiter, S., Smith, C. L., Malaki, M., Nandi, M., Gill, H., Leiper, J. M. , Vallance, P. and Selwood, D. L. (2005) Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase. Journal of Medicinal Chemistry, 48(14), pp. 4670-4678. (doi: 10.1021/jm050187a) (PMID:16000003)
Anthony, S., Leiper, J. and Vallance, P. (2005) Endogenous production of nitric oxide synthase inhibitors. Vascular Medicine, 10(2_supp), S3-S9. (doi: 10.1191/1358863x05vm595oa) (PMID:16444863)
2004
Vallance, P. and Leiper, J. (2004) Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(6), pp. 1023-30. (doi: 10.1161/01.ATV.0000128897.54893.26) (PMID:15105281)
2003
Tran, C. T.L., Leiper, J. M. and Vallance, P. (2003) The DDAH/ADMA/NOS pathway. Atherosclerosis Supplements, 4(4), pp. 33-40. (doi: 10.1016/S1567-5688(03)00032-1) (PMID:14664901)
Jones, L.C., Tran, C.T.L., Leiper, J.M. , Hingorani, A.D. and Vallance, P. (2003) Common genetic variation in a basal promoter element alters DDAH2 expression in endothelial cells. Biochemical and Biophysical Research Communications, 310(3), pp. 836-843. (doi: 10.1016/j.bbrc.2003.09.097) (PMID:14550280)
Millatt, L. J., Whitley, G. S., Li, D., Leiper, J. M. , Siragy, H. M., Carey, R. M. and Johns, R. A. (2003) Evidence for dysregulation of dimethylarginine dimethylaminohydrolase I in chronic hypoxia-induced pulmonary hypertension. Circulation, 108(12), pp. 1493-1498. (doi: 10.1161/01.CIR.0000089087.25930.FF) (PMID:12952847)
Smith, C. L., Birdsey, G. M., Anthony, S., Arrigoni, F. I., Leiper, J. M. and Vallance, P. (2003) Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype. Biochemical and Biophysical Research Communications, 308(4), pp. 984-989. (doi: 10.1016/S0006-291X(03)01507-9) (PMID:12927816)
Achan, V., Broadhead, M., Malaki, M., Whitley, G., Leiper, J. , MacAllister, R. and Vallance, P. (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(8), pp. 1455-1459. (doi: 10.1161/01.ATV.0000081742.92006.59) (PMID:12805079)
Arrigoni, F. I., Vallance, P., Haworth, S. G. and Leiper, J. M. (2003) Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation, 107(8), pp. 1195-1201. (doi: 10.1161/01.CIR.0000051466.00227.13) (PMID:12615801)
2002
Leiper, J. , Murray-Rust, J., McDonald, N. and Vallance, P. (2002) S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proceedings of the National Academy of Sciences of the United States of America, 99(21), pp. 13527-13532. (doi: 10.1073/pnas.212269799) (PMID:12370443) (PMCID:PMC129707)
Vallance, P. and Leiper, J. (2002) Blocking NO synthesis: how, where and why? Nature Reviews Drug Discovery, 1(12), pp. 939-950. (doi: 10.1038/nrd960) (PMID:12461516)
2001
Murray-Rust, J., Leiper, J. , McAlister, M., Phelan, J., Tilley, S., Santa Maria, J., Vallance, P. and McDonald, N. (2001) Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nature Structural Biology, 8(8), pp. 679-683. (doi: 10.1038/90387) (PMID:11473257)
2000
Tran, C. T.L., Fox, M. F., Vallance, P. and Leiper, J. M. (2000) Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics, 68(1), pp. 101-105. (doi: 10.1006/geno.2000.6262) (PMID:10950934)
Birdsey, G.M., Leiper, J.M. and Vallance, P. (2000) Intracellular localization of dimethylarginine dimethylaminohydrolase overexpressed in an endothelial cell line. Acta Physiologica Scandinavica, 168(1), pp. 73-79. (doi: 10.1046/j.1365-201x.2000.00672.x) (PMID:10691782)
1999
Santa Maria, J., Vallance, P., Charles, I. G. and Leiper, J. M. (1999) Identification of microbial dimethylarginine dimethylaminohydrolase enzymes. Molecular Microbiology, 33(6), pp. 1278-1279. (doi: 10.1046/j.1365-2958.1999.01580.x) (PMID:10510241)
Leiper, J. and Vallance, P. (1999) Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovascular Research, 43(3), pp. 542-548. (doi: 10.1016/S0008-6363(99)00162-5) (PMID:10690326)
1997
Leiper, J. M. and Danpure, C. J. (1997) A unique molecular basis for enzyme mistargeting in primary hyperoxaluria type 1. Clinica Chimica Acta, 266(1), pp. 39-50. (doi: 10.1016/S0009-8981(97)00165-4) (PMID:9435987)
1996
Danpure, C. J., Jennings, P. R., Leiper, J. M. , Lumb, M. J. and Oatey, P. B. (1996) Targeting of alanine: glyoxylate aminotransferase in normal individuals and its mistargeting in patients with primary hyperoxaluria type 1. Annals of the New York Academy of Sciences, 804, pp. 477-490. (doi: 10.1111/j.1749-6632.1996.tb18638.x) (PMID:8993566)
Leiper, J.M. and Danpure, C.J. (1996) The role of dimerization of alanine:glyoxylate aminotransferase 1 in its peroxisomal and mitochondrial import. Annals of the New York Academy of Sciences, 804, pp. 765-767. (PMID:8993617)
Leiper, J.M. , Harrison, G.B., Bayliss, J., Scott, J.D. and Pease, R.J. (1996) Systematic expression of the complete coding sequence of apoB-100 does not reveal transmembrane determinants. Journal of Lipid Research, 37(10), pp. 2215-2231. (PMID:8906598)
Leiper, J. M. , Oatey, P. B. and Danpure, C. J. (1996) Inhibition of alanine:glyoxylate aminotransferase 1 dimerization is a prerequisite for its peroxisome-to-mitochondrion mistargeting in primary hyperoxaluria type 1. Journal of Cell Biology, 135(4), pp. 939-951. (PMID:8922378) (PMCID:PMC2133393)
Pease, R.J. and Leiper, J.M. (1996) Regulation of hepatic apolipoprotein-B-containing lipoprotein secretion. Current Opinion in Lipidology, 7(3), pp. 132-138. (PMID:8818509)
1995
Leiper, J. M. , Birdsey, G. M. and Oatey, P. B. (1995) Peroxisomes proliferate. Trends in Cell Biology, 5(11), pp. 435-437. (doi: 10.1016/S0962-8924(00)89103-5) (PMID:14732049)
Pease, R. J., Leiper, J. M. , Harrison, G. B. and Scott, J. (1995) Studies on the translocation of the amino terminus of apolipoprotein B into the endoplasmic reticulum. Journal of Biological Chemistry, 270(13), pp. 7261-7271. (doi: 10.1074/jbc.270.13.7261) (PMID:7706266)
1994
Leiper, J.M. , Bayliss, J.D., Pease, R.J., Brett, D.J., Scott, J. and Shoulders, C.C. (1994) Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells. Journal of Biological Chemistry, 269(35), pp. 21951-21954. (PMID:8071315)
Articles
Hanson Ng, Y. Y. et al. (2024) Asymmetric dimethylarginine enables depolarizing spikes and vasospasm in mesenteric and coronary resistance arteries. Hypertension, 81(4), pp. 764-775. (doi: 10.1161/HYPERTENSIONAHA.123.22454) (PMID:38226470) (PMCID:PMC10956675)
Sri, S. et al. (2023) A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia. Cerebral Circulation - Cognition and Behavior, 5, 100189. (doi: 10.1016/j.cccb.2023.100189) (PMID:37941765) (PMCID:PMC10628644)
Dowsett, L. , Duluc, L., Higgins, E., Alghamdi, F., Fast, W., Salt, I. P. and Leiper, J. (2023) Asymmetric dimethylarginine positively modulates calcium-sensing receptor signalling to promote lipid accumulation. Cellular Signalling, 107, 110676. (doi: 10.1016/j.cellsig.2023.110676) (PMID:37028778)
Boder, P., Mary, S. , Mark, P. B. , Leiper, J. , Dominiczak, A. F. , Padmanabhan, S. , Rampold, L. and Delles, C. (2021) Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension. Journal of Hypertension, 39(8), pp. 1490-1504. (doi: 10.1097/HJH.0000000000002861) (PMID:34187999) (PMCID:PMC7611110)
Dowsett, L. , Higgins, E., Alanazi, S., Alshuwayer, N. A., Leiper, F. C. and Leiper, J. (2020) ADMA: A key player in the relationship between vascular dysfunction and inflammation in atherosclerosis. Journal of Clinical Medicine, 9(9), 3026. (doi: 10.3390/jcm9093026) (PMID:32962225) (PMCID:PMC7563400)
Zöllner, J., Lambden, S., Nasri, N. M., Leiper, J. and Johnson, M. R. (2019) Rapid onset of severe septic shock in the pregnant mouse. Biology of Reproduction, 100(2), pp. 505-513. (doi: 10.1093/biolre/ioy193) (PMID:30184059)
Lambden, S., Tomlinson, J., Piper, S., Gordon, A. C. and Leiper, J. (2018) Evidence for a protective role for the rs805305 single nucleotide polymorphism of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in septic shock through the regulation of DDAH activity. Critical Care, 22(1), 336. (doi: 10.1186/s13054-018-2277-5) (PMID:30538005) (PMCID:PMC6288902)
Bell, T., Araujo, M., Luo, Z., Tomlinson, J., Leiper, J. , Welch, W. J. and Wilcox, C. S. (2018) Regulation of fluid reabsorption in rat or mouse proximal renal tubules by asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase 1. American Journal of Physiology: Renal Physiology, 315(1), F74-F78. (doi: 10.1152/ajprenal.00560.2017) (PMID:29513072) (PMCID:PMC6087787)
Wang, C., Luo, Z., Carter, G., Wellstein, A., Jose, P. A., Tomlinson, J., Leiper, J. , Welch, W. J., Wilcox, C. S. and Wang, D. (2018) NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 314(3), R399-R406. (doi: 10.1152/ajpregu.00122.2017) (PMID:29167164)
Paul, E. J., Kalk, E., Tossell, K., Irvine, E. E., Franks, N. P., Wisden, W., Withers, D. J., Leiper, J. and Ungless, M. A. (2018) nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta. eNeuro, 5(5), ENEURO.0381-18.2018. (doi: 10.1523/ENEURO.0381-18.2018) (PMID:30456293) (PMCID:PMC6240015)
Tesfai, A. et al. (2017) Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways. PLoS ONE, 12(8), e0183025. (doi: 10.1371/journal.pone.0183025) (PMID:28813479) (PMCID:PMC5557592)
Zöllner, J., Howe, L. G., Edey, L. F., O’Dea, K. P., Takata, M., Gordon, F., Leiper, J. and Johnson, M. R. (2017) The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice. Biology of Reproduction, 97(2), pp. 258-272. (doi: 10.1093/biolre/iox076) (PMID:29044422)
Rodionov, R. N. et al. (2016) A novel pathway for metabolism of the cardiovascular risk factor homoarginine by alanine:glyoxylate aminotransferase 2. Scientific Reports, 6, 35277. (doi: 10.1038/srep35277) (PMID:27752063) (PMCID:PMC5082758)
Lange, C. et al. (2016) Dimethylarginine dimethylaminohydrolase-2 deficiency promotes vascular regeneration and attenuates pathological angiogenesis. Experimental Eye Research, 147, pp. 148-155. (doi: 10.1016/j.exer.2016.05.007) (PMID:27181226) (PMCID:PMC4912010)
Lambden, S., Martin, D., Vanezis, K., Lee, B., Tomlinson, J., Piper, S., Boruc, O., Mythen, M. and Leiper, J. (2016) Hypoxia causes increased monocyte nitric oxide synthesis which is mediated by changes in dimethylarginine dimethylaminohydrolase 2 expression in animal and human models of normobaric hypoxia. Nitric Oxide, 58, pp. 59-66. (doi: 10.1016/j.niox.2016.06.003) (PMID:27319282)
Tomlinson, J. A.P. et al. (2015) Reduced renal methylarginine metabolism protects against progressive kidney damage. Journal of the American Society of Nephrology, 26(12), pp. 3045-3059. (doi: 10.1681/ASN.2014030280) (PMID:25855779) (PMCID:PMC4657823)
DʼMello, R., Sand, C. A., Pezet, S., Leiper, J. M. , Gaurilcikaite, E., McMahon, S. B., Dickenson, A. H. and Nandi, M. (2015) Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity. Pain, 156(10), pp. 2052-2060. (doi: 10.1097/j.pain.0000000000000269) (PMID:2609843) (PMCID:PMC4770343)
Dowsett, L. et al. (2015) Endothelial dimethylarginine dimethylaminohydrolase 1 is an important regulator of angiogenesis but does not regulate vascular reactivity or hemodynamic homeostasis. Circulation, 131(25), pp. 2217-2225. (doi: 10.1161/CIRCULATIONAHA.114.015064) (PMID:25910799)
Lambden, S. et al. (2015) Dimethylarginine dimethylaminohydrolase 2 regulates nitric oxide synthesis and hemodynamics and determines outcome in polymicrobial sepsis. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(6), pp. 1382-1392. (doi: 10.1161/ATVBAHA.115.305278) (PMID:25857313)
Ahmetaj-Shala, B. et al. (2015) Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs. Circulation, 131(7), pp. 633-642. (doi: 10.1161/CIRCULATIONAHA.114.011591) (PMID:25492024) (PMCID:PMC4768634)
Starr, A., Sand, C. A., Heikal, L., Kelly, P. D., Spina, D., Crabtree, M., Channon, K. M., Leiper, J. M. and Nandi, M. (2014) Overexpression of GTP cyclohydrolase 1 feedback regulatory protein is protective in a murine model of septic shock. Shock, 42(5), pp. 432-439. (doi: 10.1097/SHK.0000000000000235) (PMID:25046538) (PMCID:PMC4851220)
Libri, V. et al. (2014) Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study. Lancet, 384(9942), pp. 504-513. (doi: 10.1016/S0140-6736(14)60382-2) (PMID:24794816)
Iannone, L., Zhao, L., Dubois, O., Duluc, L., Rhodes, C. J., Wharton, J., Wilkins, M. R., Leiper, J. and Wojciak-Stothard, B. (2014) miR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia. Biochemical Journal, 462(1), pp. 103-112. (doi: 10.1042/BJ20140486) (PMID:24895913)
Wang, Z. et al. (2014) Pharmacological inhibition of DDAH1 improves survival, haemodynamics and organ function in experimental septic shock. Biochemical Journal, 460(2), pp. 309-316. (doi: 10.1042/BJ20131666) (PMID:24611830)
Ghebremariam, Y. T., LePendu, P., Lee, J. C., Erlanson, D. A., Slaviero, A., Shah, N. H., Leiper, J. M. and Cooke, J. P. (2014) Response to letters regarding article, "Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine". Circulation, 129(13), e428-e428. (doi: 10.1161/CIRCULATIONAHA.114.009343) (PMID:24687654) (PMCID:PMC4105215)
Tsang, H. et al. (2013) Role of asymmetric methylarginine and connexin 43 in the regulation of pulmonary endothelial function. Pulmonary Circulation, 3(3), pp. 675-691. (doi: 10.1086/674440) (PMID:24618552) (PMCID:PMC4070793)
Ghebremariam, Y. T., LePendu, P., Lee, J. C., Erlanson, D. A., Slaviero, A., Shah, N. H., Leiper, J. and Cooke, J. P. (2013) Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation, 128(8), pp. 845-853. (doi: 10.1161/CIRCULATIONAHA.113.003602) (PMID:23825361) (PMCID:PMC3838201)
Caplin, B., Wang, Z., Slaviero, A., Tomlinson, J., Dowsett, L. , Delahaye, M., Salama, A., Wheeler, D. C. and Leiper, J. (2012) Alanine-glyoxylate aminotransferase-2 metabolizes endogenous methylarginines, regulates NO, and controls blood pressure. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(12), pp. 2892-2900. (doi: 10.1161/ATVBAHA.112.254078) (PMID:23023372)
Nandi, M., Kelly, P., Torondel, B., Wang, Z., Starr, A., Ma, Y., Cunningham, P., Stidwill, R. and Leiper, J. (2012) Genetic and pharmacological inhibition of dimethylarginine dimethylaminohydrolase 1 is protective in endotoxic shock. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(11), pp. 2589-97. (doi: 10.1161/ATVBAHA.112.300232) (PMID:22995517)
Caplin, B. and Leiper, J. (2012) Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators? Arteriosclerosis, Thrombosis, and Vascular Biology, 32(6), pp. 1343-1353. (doi: 10.1161/ATVBAHA.112.247726) (PMID:22460557) (PMCID:PMC3975829)
Woods, A., Leiper, J. M. and Carling, D. (2012) The role of ATM in response to metformin treatment and activation of AMPK [Letter]. Nature Genetics, 44(4), pp. 360-361. (doi: 10.1038/ng.2235) (PMID:22456733)
Boult, J. K.R., Walker-Samuel, S., Jamin, Y., Leiper, J. M. , Whitley, G. S. J. and Robinson, S. P. (2011) Active site mutant dimethylarginine dimethylaminohydrolase 1 expression confers an intermediate tumour phenotype in C6 gliomas. Journal of Pathology, 225(3), pp. 344-352. (doi: 10.1002/path.2904) (PMID:21590769)
Leiper, J. and Nandi, M. (2011) The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nature Reviews Drug Discovery, 10(4), pp. 277-291. (doi: 10.1038/nrd3358) (PMID:21455237)
Pullamsetti, S. S. et al. (2011) cAMP phosphodiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases. Circulation, 123(11), pp. 1194-204. (doi: 10.1161/CIRCULATIONAHA.110.941484) (PMID:21382892)
Pullamsetti, S. S. et al. (2011) The role of dimethylarginine dimethylaminohydrolase in idiopathic pulmonary fibrosis. Science Translational Medicine, 3(87), 87ra53. (doi: 10.1126/scitranslmed.3001725) (PMID:21677199)
Lakhani, K., Kay, A. R., Leiper, J. , Barry, J. A. and Hardiman, P. J. (2011) Symmetric dimethylarginine (SDMA) is raised in women with polycystic ovary syndrome: A pilot study. Journal of Obstetrics and Gynaecology, 31(5), pp. 417-419. (doi: 10.3109/01443615.2011.569779) (PMID:21627426)
Gray, G. A., Patrizio, M., Sherry, L., Miller, A. A. , Malaki, M., Wallace, A. F., Leiper, J. M. and Vallance, P. (2010) Immunolocalisation and activity of DDAH I and II in the heart and modification post-myocardial infarctioN. Acta Histochemica, 112(5), pp. 413-423. (doi: 10.1016/j.acthis.2009.02.009) (PMID:19481782)
Torondel, B., Nandi, M., Kelly, P., Wojciak-Stothard, B., Fleming, I. and Leiper, J. (2010) Adenoviral-mediated overexpression of DDAH improves vascular tone regulation. Vascular Medicine, 15(3), pp. 205-213. (doi: 10.1177/1358863X09360264) (PMID:20219849)
Caplin, B. et al. (2010) Circulating methylarginine levels and the decline in renal function in patients with chronic kidney disease are modulated by DDAH1 polymorphisms. Kidney International, 77(5), pp. 459-467. (doi: 10.1038/ki.2009.463) (PMID:20010544)
Ivashchenko, C. Y., Bradley, B. T., Ao, Z., Leiper, J. , Vallance, P. and Johns, D. J. (2010) Regulation of the ADMA-DDAH system in endothelial cells: a novel mechanism for the sterol response element binding proteins, SREBP1c and -2. American Journal of Physiology: Heart and Circulatory Physiology, 298(1), H251-H258. (doi: 10.1152/ajpheart.00195.2009) (PMID:19915177) (PMCID:PMC2806130)
Arrigoni, F., Ahmetaj, B. and Leiper, J. (2010) The Biology and therapeutic potential of the DDAH/ADMA pathway. Current Pharmaceutical Design, 16(37), pp. 4089-4102. (doi: 10.2174/138161210794519246) (PMID:21247398)
Breckenridge, R. A., Kelly, P., Nandi, M., Vallance, P. J., Ohun, T. J. and Leiper, J. (2010) A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development. International Journal of Developmental Biology, 54(1), pp. 215-226. (doi: 10.1387/ijdb.072356rb) (PMID:19757398)
Fiedler, L. R., Bachetti, T., Leiper, J. , Zachary, I., Chen, L., Renné, T. and Wojciak-Stothard, B. (2009) The ADMA/DDAH pathway regulates VEGF-mediated angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(12), pp. 2117-2124. (doi: 10.1161/ATVBAHA.109.194035) (PMID:19778944)
Wojciak-Stothard, B., Torondel, B., Zhao, L., Renne, T. and Leiper, J. M. (2009) Modulation of Rac1 activity by ADMA/DDAH regulates pulmonary endothelial barrier function. Molecular Biology of the Cell, 20(1), pp. 33-42. (doi: 10.1091/mbc.E08-04-0395) (PMID:18923147) (PMCID:PMC2613095)
Nandi, M., Kelly, P., Vallance, P. and Leiper, J. (2008) Over-expression of GTP-cyclohydrolase 1 feedback regulatory protein attenuates LPS and cytokine-stimulated nitric oxide production. Vascular Medicine, 13(1), pp. 29-36. (doi: 10.1177/1358863X07085916)
Onozato, M. L., Tojo, A., Leiper, J. , Fujita, T., Palm, F. and Wilcox, C. S. (2008) Expression of NG,NG-dimethylarginine dimethylaminohydrolase and protein arginine N-methyltransferase isoforms in diabetic rat kidney: effects of angiotensin II receptor blockers. Diabetes, 57(1), pp. 172-180. (doi: 10.2337/db06-1772) (PMID:17909098)
Wojciak‐Stothard, B. and Leiper, J. (2008) Rho GTPases and hypoxia in pulmonary vascular endothelial cells. Methods in Enzymology, 439, pp. 267-283. (doi: 10.1016/S0076-6879(07)00420-X) (PMID:18374171)
Wang, D. et al. (2007) Isoform-specific regulation by N(G),N(G)-dimethylarginine dimethylaminohydrolase of rat serum asymmetric dimethylarginine and vascular endothelium-derived relaxing factor/NO. Circulation Research, 101(6), pp. 627-35. (doi: 10.1161/CIRCRESAHA.107.158915) (PMID:17673667)
Hartzoulakis, B. et al. (2007) Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis. Bioorganic and Medicinal Chemistry Letters, 17(14), pp. 3953-3956. (doi: 10.1016/j.bmcl.2007.04.095) (PMID:17543521)
Wojciak-Stothard, B., Torondel, B., Tsang, L. Y. F., Fleming, I., Fisslthaler, B., Leiper, J. M. and Vallance, P. (2007) The ADMA/DDAH pathway is a critical regulator of endothelial cell motility. Journal of Cell Science, 120(6), pp. 929-942. (doi: 10.1242/jcs.002212) (PMID:17327280)
Leiper, J. et al. (2007) Disruption of methylarginine metabolism impairs vascular homeostasis. Nature Medicine, 13(2), pp. 198-203. (doi: 10.1038/nm1543) (PMID:17273169)
Bulau, P., Zakrzewicz, D., Kitowska, K., Leiper, J. , Gunther, A., Grimminger, F. and Eickelberg, O. (2007) Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA. American Journal of Physiology: Lung Cellular and Molecular Physiology, 292(1), L18-L24. (doi: 10.1152/ajplung.00076.2006) (PMID:16891395)
Mookerjee, R. P. et al. (2007) Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis. Hepatology, 45(1), pp. 62-71. (doi: 10.1002/hep.21491) (PMID:17187433)
Leiper, J. and Vallance, P. (2006) New tricks from an old dog: nitric oxide-independent effects of dimethylarginine dimethylaminohydrolase. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(7), pp. 1419-1420. (doi: 10.1161/01.ATV.0000229598.55602.17) (PMID:16794231)
Nandi, M., Leiper, J. , Arrigoni, F., Hislop, A., Vallance, P. and Haworth, S. (2006) Developmental regulation of GTP-CH1 in the porcine lung and its relationship to pulmonary vascular relaxation. Pediatric Research, 59(6), pp. 767-772. (doi: 10.1203/01.pdr.0000219301.19958.a0) (PMID:16641207)
Leiper, J. M. (2005) The DDAH-ADMA-NOS pathway. Therapeutic Drug Monitoring, 27(6), pp. 744-746. (doi: 10.1097/01.ftd.0000179849.42395.11) (PMID:16404814)
Smith, C. L., Anthony, S., Hubank, M., Leiper, J. M. and Vallance, P. (2005) Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA. PLoS Medicine, 2(10), e264. (doi: 10.1371/journal.pmed.0020264) (PMID:16190779) (PMCID:PMC1240048)
Vallance, P. and Leiper, J. (2005) Asymmetric dimethylarginine and kidney disease: marker or mediator? Journal of the American Society of Nephrology, 16(8), pp. 2254-2256. (doi: 10.1681/ASN.2005050539) (PMID:15987745)
Rossiter, S., Smith, C. L., Malaki, M., Nandi, M., Gill, H., Leiper, J. M. , Vallance, P. and Selwood, D. L. (2005) Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase. Journal of Medicinal Chemistry, 48(14), pp. 4670-4678. (doi: 10.1021/jm050187a) (PMID:16000003)
Anthony, S., Leiper, J. and Vallance, P. (2005) Endogenous production of nitric oxide synthase inhibitors. Vascular Medicine, 10(2_supp), S3-S9. (doi: 10.1191/1358863x05vm595oa) (PMID:16444863)
Vallance, P. and Leiper, J. (2004) Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(6), pp. 1023-30. (doi: 10.1161/01.ATV.0000128897.54893.26) (PMID:15105281)
Tran, C. T.L., Leiper, J. M. and Vallance, P. (2003) The DDAH/ADMA/NOS pathway. Atherosclerosis Supplements, 4(4), pp. 33-40. (doi: 10.1016/S1567-5688(03)00032-1) (PMID:14664901)
Jones, L.C., Tran, C.T.L., Leiper, J.M. , Hingorani, A.D. and Vallance, P. (2003) Common genetic variation in a basal promoter element alters DDAH2 expression in endothelial cells. Biochemical and Biophysical Research Communications, 310(3), pp. 836-843. (doi: 10.1016/j.bbrc.2003.09.097) (PMID:14550280)
Millatt, L. J., Whitley, G. S., Li, D., Leiper, J. M. , Siragy, H. M., Carey, R. M. and Johns, R. A. (2003) Evidence for dysregulation of dimethylarginine dimethylaminohydrolase I in chronic hypoxia-induced pulmonary hypertension. Circulation, 108(12), pp. 1493-1498. (doi: 10.1161/01.CIR.0000089087.25930.FF) (PMID:12952847)
Smith, C. L., Birdsey, G. M., Anthony, S., Arrigoni, F. I., Leiper, J. M. and Vallance, P. (2003) Dimethylarginine dimethylaminohydrolase activity modulates ADMA levels, VEGF expression, and cell phenotype. Biochemical and Biophysical Research Communications, 308(4), pp. 984-989. (doi: 10.1016/S0006-291X(03)01507-9) (PMID:12927816)
Achan, V., Broadhead, M., Malaki, M., Whitley, G., Leiper, J. , MacAllister, R. and Vallance, P. (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(8), pp. 1455-1459. (doi: 10.1161/01.ATV.0000081742.92006.59) (PMID:12805079)
Arrigoni, F. I., Vallance, P., Haworth, S. G. and Leiper, J. M. (2003) Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation, 107(8), pp. 1195-1201. (doi: 10.1161/01.CIR.0000051466.00227.13) (PMID:12615801)
Leiper, J. , Murray-Rust, J., McDonald, N. and Vallance, P. (2002) S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proceedings of the National Academy of Sciences of the United States of America, 99(21), pp. 13527-13532. (doi: 10.1073/pnas.212269799) (PMID:12370443) (PMCID:PMC129707)
Vallance, P. and Leiper, J. (2002) Blocking NO synthesis: how, where and why? Nature Reviews Drug Discovery, 1(12), pp. 939-950. (doi: 10.1038/nrd960) (PMID:12461516)
Murray-Rust, J., Leiper, J. , McAlister, M., Phelan, J., Tilley, S., Santa Maria, J., Vallance, P. and McDonald, N. (2001) Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nature Structural Biology, 8(8), pp. 679-683. (doi: 10.1038/90387) (PMID:11473257)
Tran, C. T.L., Fox, M. F., Vallance, P. and Leiper, J. M. (2000) Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics, 68(1), pp. 101-105. (doi: 10.1006/geno.2000.6262) (PMID:10950934)
Birdsey, G.M., Leiper, J.M. and Vallance, P. (2000) Intracellular localization of dimethylarginine dimethylaminohydrolase overexpressed in an endothelial cell line. Acta Physiologica Scandinavica, 168(1), pp. 73-79. (doi: 10.1046/j.1365-201x.2000.00672.x) (PMID:10691782)
Santa Maria, J., Vallance, P., Charles, I. G. and Leiper, J. M. (1999) Identification of microbial dimethylarginine dimethylaminohydrolase enzymes. Molecular Microbiology, 33(6), pp. 1278-1279. (doi: 10.1046/j.1365-2958.1999.01580.x) (PMID:10510241)
Leiper, J. and Vallance, P. (1999) Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovascular Research, 43(3), pp. 542-548. (doi: 10.1016/S0008-6363(99)00162-5) (PMID:10690326)
Leiper, J. M. and Danpure, C. J. (1997) A unique molecular basis for enzyme mistargeting in primary hyperoxaluria type 1. Clinica Chimica Acta, 266(1), pp. 39-50. (doi: 10.1016/S0009-8981(97)00165-4) (PMID:9435987)
Danpure, C. J., Jennings, P. R., Leiper, J. M. , Lumb, M. J. and Oatey, P. B. (1996) Targeting of alanine: glyoxylate aminotransferase in normal individuals and its mistargeting in patients with primary hyperoxaluria type 1. Annals of the New York Academy of Sciences, 804, pp. 477-490. (doi: 10.1111/j.1749-6632.1996.tb18638.x) (PMID:8993566)
Leiper, J.M. and Danpure, C.J. (1996) The role of dimerization of alanine:glyoxylate aminotransferase 1 in its peroxisomal and mitochondrial import. Annals of the New York Academy of Sciences, 804, pp. 765-767. (PMID:8993617)
Leiper, J.M. , Harrison, G.B., Bayliss, J., Scott, J.D. and Pease, R.J. (1996) Systematic expression of the complete coding sequence of apoB-100 does not reveal transmembrane determinants. Journal of Lipid Research, 37(10), pp. 2215-2231. (PMID:8906598)
Leiper, J. M. , Oatey, P. B. and Danpure, C. J. (1996) Inhibition of alanine:glyoxylate aminotransferase 1 dimerization is a prerequisite for its peroxisome-to-mitochondrion mistargeting in primary hyperoxaluria type 1. Journal of Cell Biology, 135(4), pp. 939-951. (PMID:8922378) (PMCID:PMC2133393)
Pease, R.J. and Leiper, J.M. (1996) Regulation of hepatic apolipoprotein-B-containing lipoprotein secretion. Current Opinion in Lipidology, 7(3), pp. 132-138. (PMID:8818509)
Leiper, J. M. , Birdsey, G. M. and Oatey, P. B. (1995) Peroxisomes proliferate. Trends in Cell Biology, 5(11), pp. 435-437. (doi: 10.1016/S0962-8924(00)89103-5) (PMID:14732049)
Pease, R. J., Leiper, J. M. , Harrison, G. B. and Scott, J. (1995) Studies on the translocation of the amino terminus of apolipoprotein B into the endoplasmic reticulum. Journal of Biological Chemistry, 270(13), pp. 7261-7271. (doi: 10.1074/jbc.270.13.7261) (PMID:7706266)
Leiper, J.M. , Bayliss, J.D., Pease, R.J., Brett, D.J., Scott, J. and Shoulders, C.C. (1994) Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells. Journal of Biological Chemistry, 269(35), pp. 21951-21954. (PMID:8071315)
Book Sections
Leiper, J. (2019) Nitric oxide. In: Touyz, R. M. and Delles, C. (eds.) Textbook of Vascular Medicine. Springer: Cham, pp. 117-126. ISBN 9783030164805 (doi: 10.1007/978-3-030-16481-2_11)
Grants
Grants and Awards listed are those received whilst working with the University of Glasgow.
- Reducing with Metformin Adverse Vascular Lesions (REMOVAL) Trial Follow-up - Identifying those at risk of Type 1 Diabetes-associated vascular complications
The Novo Nordisk UK Research Foundation
2024 - 2024
- Investigating calcium-sensing receptor mediated sex differences in cardiometabolic disease
British Heart Foundation
2024 - 2027
- Regulation of Adipose Tissue Metabolism by Assymetric Dimethylarginine
Diabetes UK
2022 - 2025
- Asymmetric dimethylarginine signalling via the calcium sensing receptor in the vascular and metabolic complications of type 2 diabetes
British Heart Foundation
2021 - 2024
- Defining the role of the ADMA-DDAH1 pathway in ischaemic stroke
British Heart Foundation
2020 - 2023
- Using the Endo-Ribotag mouse to identify targtes of ADMA in vascular disease
Rosetrees Trust
2019 - 2020
- BHF Centre of Excellence
British Heart Foundation (BHF)
2019 - 2024
- BHF Centre of Excellence
British Heart Foundation
2019 - 2024
Supervision
- Gerganova, Gabriela
Inflammatory mechanisms after ischaemic stroke: roles of CNS border-associated macrophages (BAMs) and dimethylarginine dimethylaminohydrolase (DDAH2)