B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice

Published in the Journal of the American Heart Association, this study evaluated the cardioprotective effects of B7-33 in a myocardial ischemia-reperfusion model in mice, simulating the conditions of an acute myocardial infarction followed by restoration of blood flow. B7-33 was administered at the time of reperfusion to assess its potential as an adjunctive post-infarction therapy.

The results were striking: B7-33 reduced the infarct area from 45.32% to 21.99% of the area at risk — a reduction of more than 50% in the extent of myocardial damage. This cardioprotection was accompanied by significant preservation of left ventricular fractional shortening, an echocardiographic parameter reflecting the heart's contractile capacity.

Beyond acute protection, B7-33 demonstrated beneficial effects on cardiac remodeling assessed in the weeks following infarction. Adverse remodeling — the process by which the heart dilates and loses function after an infarction — was significantly attenuated in treated animals, with reduced interstitial fibrosis and less ventricular dilation. Mechanistically, these effects were associated with a reduction in inflammatory markers and attenuation of pro-fibrotic pathways.

This study significantly expanded the therapeutic potential of B7-33 beyond the vasoprotection previously demonstrated, positioning it as a candidate for acute cardioprotection and prevention of post-infarction heart failure. The functionally selective activation of the RXFP1 receptor by B7-33 offers an innovative therapeutic approach to ischemic cardiovascular disease.