Apelin - 13 increases myocardial progenitor cells and improves repair of post - 2 myocardial infarction

27 Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and has beneficial 28 effects against myocardial ischemia/reperfusion injury. Little is known about the role of 29 apelin in the homing of vascular progenitor cells (PCs) and cardiac functional recovery 30 post-myocardial infarction (MI). The present study investigates whether apelin affects PCs 31 homing to the infarcted myocardium thereby mediating repair and functional recovery post32 MI. Mice were infarcted by coronary artery ligation and apelin-13 (1 mg/kg.d) was injected 33 for three days prior to MI and for 14 days post MI. Homing of vascular progenitor cell 34 (CD133/c-kit/Sca1, CD133/SDF-1α and CD133/CXCR4) into the ischemic area were 35 examined. Myocardial Akt, eNOS, VEGF, Jagged1, Notch3, SDF-1α and CXCR4 36 expression were assessed at 24 hours and 14 days post-MI. Functional analyses were 37 performed at day 14 after MI. Mice receiving apelin-13 treatment demonstrated 38 upregulation of SDF-1α/CXCR4 expression and dramatically increased the number of 39 CD133/c-kit/Sca1, CD133/SDF-1α and c-kit/CXCR4 cells in the infarcted hearts. 40 Apelin-13 also significantly increased Akt and eNOS phosphorylation and upregulated 41 VEGF, Jagged1, Notch3 expression in the ischemic hearts. This was accompanied by a 42 significant reduction of myocardial apoptosis. Further, treatment with apelin-13 promoted 43 myocardial angiogenesis, attenuated cardiac fibrosis and hypertrophy together with a 44 significant improvement of cardiac function at 14 days post-MI mice. Apelin-13 increases 45 angiogenesis and improves cardiac repair following MI by a mechanism involving 46 upregulation of SDF-1α/CXCR4 and homing of vascular progenitor cells. 47