The actions of relaxin on the human cardiovascular system

被引：82

作者：

Sarwar, Mohsin ^{[1
]}

Du, Xiao-Jun ^{[2
]}

Dschietzig, Thomas B. ^{[3
,4
,5
]}

Summers, Roger J. ^{[1
]}

机构：

[1] Monash Inst Pharmaceut Sci, Drug Discovery Biol, Parkville, Vic, Australia

[2] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia

[3] Immundiagnostik AG, Bensheim, Germany

[4] Charite, Med Clin Cardiol & Angiol, Campus Mitte, Berlin, Germany

[5] Relaxera Pharmazeut Gesell mbH & Co KG, Bensheim, Germany

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2017年 / 174卷 / 10期

基金：

英国医学研究理事会; 澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

ACUTE HEART-FAILURE; ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE PATHWAY; PREGNANCY HORMONE RELAXIN; SPONTANEOUSLY HYPERTENSIVE-RATS; RENAL INTERSTITIAL FIBROSIS; REVERSES CARDIAC FIBROSIS; LOWER REPRODUCTIVE-TRACT; SYSTOLIC BLOOD-PRESSURE; B RECEPTOR EXPRESSION;

D O I：

10.1111/bph.13523

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

The insulin-like peptide relaxin, originally identified as a hormone of pregnancy, is now known to exert a range of pleiotropic effects including vasodilatory, anti-fibrotic, angiogenic, anti-apoptotic and anti-inflammatory effects in both males and females. Relaxin produces these effects by binding to a cognate receptor RXFP1 and activating a variety of signalling pathways including cAMP, cGMP and MAPKs as well as by altering gene expression of TGF-beta, MMPs, angiogenic growth factors and endothelin receptors. The peptide has been shown to be effective in halting or reversing many of the adverse effects including fibrosis in animal models of cardiovascular disease including ischaemia/reperfusion injury, myocardial infarction, hypertensive heart disease and cardiomyopathy. Relaxin given to humans is safe and produces favourable haemodynamic changes. Serelaxin, the recombinant form of relaxin, is now in extended phase III clinical trials for the treatment of acute heart failure. Previous clinical studies indicated that a 48 h infusion of relaxin improved 180 day mortality, yet the mechanism underlying this effect is not clear. This article provides an overview of the cellular mechanism of effects of relaxin and summarizes its beneficial actions in animal models and in the clinic. We also hypothesize potential mechanisms for the clinical efficacy of relaxin, identify current knowledge gaps and suggest new ways in which relaxin could be useful therapeutically.

引用

页码：933 / 949

页数：17

共 169 条

[1]

Relaxin induces matrix-metalloproteinases-9 and-13 via RXFP1: Induction of MMP-9 involves the PI3K, ERK, Akt and PKC-ζ pathways [J].

Ahmad, Nisar ;

Wang, Wei ;

Nair, Remi ;

Kapila, Sunil .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2012, 363 (1-2) :46-61

[2]

THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors [J].

Alexander, Stephen P. H. ;

Davenport, Anthony P. ;

Kelly, Eamonn ;

Marrion, Neil ;

Peters, John A. ;

Benson, Helen E. ;

Faccenda, Elena ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Davies, Jamie A. ;

Aldrich, R. ;

Attali, B. ;

Back, M. ;

Barnes, N. M. ;

Bathgate, R. ;

Beart, P. M. ;

Becirovic, E. ;

Biel, M. ;

Birdsall, N. J. ;

Boison, D. ;

Brauner-Osborne, H. ;

Broeer, S. ;

Bryant, C. ;

Burnstock, G. ;

Burris, T. ;

Cain, D. ;

Calo, G. ;

Chan, S. L. ;

Chandy, K. G. ;

Chiang, N. ;

Christakos, S. ;

Christopoulos, A. ;

Chun, J. J. ;

Chung, J. -J. ;

Clapham, D. E. ;

Connor, M. A. ;

Coons, L. ;

Cox, H. M. ;

Dautzenberg, F. M. ;

Dent, G. ;

Douglas, S. D. ;

Dubocovich, M. L. ;

Edwards, D. P. ;

Farndale, R. ;

Fong, T. M. ;

Forrest, D. ;

Fowler, C. J. ;

Fuller, P. ;

Gainetdinov, R. R. .

BRITISH JOURNAL OF PHARMACOLOGY, 2015, 172 (24) :5744-5869

[3]

THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Enzymes [J].

Alexander, Stephen P. H. ;

Fabbro, Doriano ;

Kelly, Eamonn ;

Marrion, Neil ;

Peters, John A. ;

Benson, Helen E. ;

Faccenda, Elena ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Davies, Jamie A. ;

Aldrich, R. ;

Attali, B. ;

Back, M. ;

Barnes, N. M. ;

Bathgate, R. ;

Beart, P. M. ;

Becirovic, E. ;

Biel, M. ;

Birdsall, N. J. ;

Boison, D. ;

Brauner-Osborne, H. ;

Broeer, S. ;

Bryant, C. ;

Burnstock, G. ;

Burris, T. ;

Cain, D. ;

Calo, G. ;

Chan, S. L. ;

Chandy, K. G. ;

Chiang, N. ;

Christakos, S. ;

Christopoulos, A. ;

Chun, J. J. ;

Chung, J. -J. ;

Clapham, D. E. ;

Connor, M. A. ;

Coons, L. ;

Cox, H. M. ;

Dautzenberg, F. M. ;

Dent, G. ;

Douglas, S. D. ;

Dubocovich, M. L. ;

Edwards, D. P. ;

Farndale, R. ;

Fong, T. M. ;

Forrest, D. ;

Fowler, C. J. ;

Fuller, P. ;

Gainetdinov, R. R. .

BRITISH JOURNAL OF PHARMACOLOGY, 2015, 172 (24) :6024-6109

[4]

THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Nuclear hormone receptors [J].

Alexander, Stephen P. H. ;

Cidlowski, John A. ;

Kelly, Eamonn ;

Marrion, Neil ;

Peters, John A. ;

Benson, Helen E. ;

Faccenda, Elena ;

Pawson, Adam J. ;

Sharman, Joanna L. ;

Southan, Christopher ;

Davies, Jamie A. ;

Aldrich, R. ;

Attali, B. ;

Back, M. ;

Barnes, N. M. ;

Bathgate, R. ;

Beart, P. M. ;

Becirovic, E. ;

Biel, M. ;

Birdsall, N. J. ;

Boison, D. ;

Brauner-Osborne, H. ;

Broeer, S. ;

Bryant, C. ;

Burnstock, G. ;

Burris, T. ;

Cain, D. ;

Calo, G. ;

Chan, S. L. ;

Chandy, K. G. ;

Chiang, N. ;

Christakos, S. ;

Christopoulos, A. ;

Chun, J. J. ;

Chung, J. -J. ;

Clapham, D. E. ;

Connor, M. A. ;

Coons, L. ;

Cox, H. M. ;

Dautzenberg, F. M. ;

Dent, G. ;

Douglas, S. D. ;

Dubocovich, M. L. ;

Edwards, D. P. ;

Farndale, R. ;

Fong, T. M. ;

Forrest, D. ;

Fowler, C. J. ;

Fuller, P. ;

Gainetdinov, R. R. .

BRITISH JOURNAL OF PHARMACOLOGY, 2015, 172 (24) :5956-5978

[5]

Relaxin Protects Rat Lungs from Ischemia-Reperfusion Injury via Inducible NO Synthase: Role of ERK-1/2, PI3K, and Forkhead Transcription Factor FKHRL1 [J].

Alexiou, Konstantin ;

Wilbring, Manuel ;

Matschke, Klaus ;

Dschietzig, Thomas .

PLOS ONE, 2013, 8 (09)

[6]

Relaxin activates the L-arginine nitric oxide pathway in vascular smooth muscle cells in culture [J].

Bani, D ;

Failli, P ;

Bello, MG ;

Thiemermann, C ;

Sacchi, TB ;

Bigazzi, M ;

Masini, E .

HYPERTENSION, 1998, 31 (06) :1240-1247

[7]

BANI D, 1995, CANCER RES, V55, P5272

[8]

BANI D, 1995, LAB INVEST, V73, P709

[9]

Bani D, 1998, AM J PATHOL, V152, P1367

[10]

Inhibitory effects of relaxin on human basophils activated by stimulation of the Fcε receptor.: The role of nitric oxide [J].

Bani, D ;

Baronti, R ;

Vannacci, A ;

Bigazzi, M ;

Sacchi, TB ;

Mannaioni, PF ;

Masini, E .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2002, 2 (08) :1195-1204

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