In mice, a lab-made peptide called B7-33, which mimics part of the natural hormone relaxin, helped protect the heart after a simulated heart attack. It made the damaged area smaller and kept the heart pumping better, likely by helping heart cells survive and reducing stress inside the cells.

Background Human relaxin-2 is a peptide hormone capable of pleiotropic effects in several organ systems. Its recombinant formulation (serelaxin) has been demonstrated to reduce infarct size and prevent excessive scar formation in animal models of cardiac ischemia-reperfusion injury. B7-33, a synthetically designed peptide analogous to B-chain of relaxin-2, invokes signaling at relaxin family peptide receptor 1 (cognate receptor for relaxin-2) by preferentially phosphorylating the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2. We sought to investigate the effects of B7-33 treatment post ischemia-reperfusion injury in mice. Methods and Results Adult male CD1 mice were subjected to ischemia-reperfusion via ligation of left anterior descending artery for 30&#xa0;minutes, followed by 24&#xa0;hours or 7&#xa0;days of reperfusion. Echocardiography was performed to assess cardiac function, and cardiac tissue was stained to determine infarct size at 24&#xa0;hours. B7-33 significantly reduced infarct size (21.99% versus 45.32%; <i>P</i>=0.02) and preserved fractional shortening (29% versus 23%; <i>P</i>=0.02) compared with vehicle. The difference in fractional shortening further increased at 7&#xa0;days post myocardial infarction (29% versus 20% for B7-33 and vehicle groups, respectively). In vitro<i>,</i> primary cardiomyocytes were isolated from adult hearts and subjected to simulated ischemia-reperfusion injury (simulated ischemia reoxygenation). B7-33 (50 and 100&#xa0;nmol/L) improved cell survival and reduced the expression of GRP78 (glucose regulated protein), an endoplasmic reticulum stress marker. Subsequently, B7-33 (100&#xa0;nmol/L) reduced tunicamycin (2.5&#xa0;&#x3bc;g/mL) induced upregulation of GRP78 in an extracellular signal-regulated kinase 1/2-dependent manner. Conclusions B7-33 confers acute cardioprotection and limits myocardial infarction-related adverse remodeling in mice by attenuating cardiomyocyte death and endoplasmic reticulum stress as well as preserving cardiac function.