Endothelial cell-derived MYDGF alleviates cardiomyocyte injury in rats after ischemia/reperfusion

Crosstalk in the heart is essential for normal cardiac development and disease progression. We explored the potential cardioprotective effects of endothelial cell-derived myeloid-derived growth factor (MYDGF) on the myocardium during ischemia/reperfusion (I/R) injury.

Rat H9C2 cardiomyocytes and hypoxia/reoxygenation (H/R)-induced H9C2 cells were exposed to supernatants from H/R-induced H9C2 cells or cardiac microvascular endothelial cells (CMECs). Cell death and viability were assessed using LDH and MTS assays, respectively. Apoptosis was measured by FACS analysis. Proteomic analysis was performed using iTRAQ technology. In an in vivo rat I/R model, the myocardial infarction area was assessed by TTC and Evans blue double staining. Bax and Bcl-2 protein levels were analyzed by Western blot. MYDGF, caspase 3 and caspase 8 localizations were determined via immunohistochemical staining.

The supernatant from H/R-induced CMECs alleviated injury to H9C2 cells. Among the 474 differentially expressed proteins identified, MYDGF expression was notably increased, especially under the H8h/R2h conditions. MYDGF expression was also elevated in the vascular endothelium of I1h/R24h rats. MYDGF protected H9C2 cells and neonatal rat ventricular myocytes (NRVMs) from H8h/R2h-induced injury in vitro and ameliorated I1h/R24h-induced injury in vivo. This protective effect was further confirmed by the injection of AAV9-MYDGF into the left ventricular wall. Conversely, interfering with MYDGF expression in heart endothelial cells with AAV-Tie-2-shMYDGF exacerbated myocardial injury after I1h/R24h in rats.

This study elucidates the cardioprotective role of endothelial cell-derived MYDGF in preventing cardiomyocyte injury. We expect to observe the potential therapeutic effects of MYDGF on I/R injury in the future.