Reversal of cardiac fibrosis and related dysfunction by relaxin.
As a hallmark of heart disease, cardiac fibrosis contributes to the development of heart failure and arrhythmias and forms a key therapeutic target. There is a major unmet need for selective, potent, and safe antifibrotic drugs. Earlier studies revealed a cardiac fibrosis phenotype in relaxin-1-deficient mice. Recent studies in several rodent models of cardiac fibrosis have documented reversal of fibrosis by treatment with relaxin peptide or virally mediated relaxin gene delivery. In mice with surgically induced transmural myocardial infarction, relaxin therapy inhibited scar density. In these studies, however, functional benefits achieved by relaxin therapy were limited or less explored. Collectively, there is good experimental evidence that relaxin is able to reverse cardiac fibrosis due to distinct mechanisms. Future research needs to explore functional improvement following fibrosis reversal by relaxin and the usefulness of relaxin in antiarrhythmic or stem cell-based therapy.
Du
Xiao-Jun
XJ
Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, University of Melbourne, Melbourne, Australia. xiaojun.du@bakeridi.edu.au
Xu
Qi
Q
Lekgabe
Edna
E
Gao
Xiao-Ming
XM
Kiriazis
Helen
H
Moore
Xiao-Lei
XL
Dart
Anthony M
AM
Tregear
Geoffrey W
GW
Bathgate
Ross A D
RA
Samuel
Chrishan S
CS
D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy* / Q000517:prevention & control*; D006331:Heart Diseases / Q000188:drug therapy* / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D051381:Rats; D012065:Relaxin / Q000627:therapeutic use*
D012065:Relaxin