Apelin Enhances Cardiac Neovascularization After Myocardial Infarction by Recruiting Aplnr+ Circulating Cells

Abstract

Rationale: Neovascularization stimulated by local or recruited stem cells after ischemia is a key process that salvages damaged tissue and shows similarities with embryonic vascularization. Apelin receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular development. However, the role of apelin signaling in stem cell recruitment after ischemia is unknown.Objective: To investigate the role of apelin signaling in recruitment after ischemia. Methods and Results:

Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury

“…Two recent echocardiography-based studies suggest that A13 maintains cardiac function over a 2-week period [11,12]. Our current investigation provides detailed analysis of cardiac function by both cardiac MRI and invasive PV loop over an 8-week period.…”

“…In addition, the Apelin-APJ system influences the heart field development and cardiac differentiation of pluripotent stem cells as we have reported recently [9,10]. Other groups have reported that A13 may modulate endogenous stem cell function after acute myocardial injury (AMI) [11,12]. However, there is no definitive tissue characterization of the restorative effects on the injured myocardium.…”

Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction

“…This observation is in line with the hypothesis that the activation of lymphatic vessels in early-phase MI may have a beneficial role in stimulating lymphangiogenic growth in the chronic phase of MI. Apelin has a pleiotropic action, facilitating cardiomyocyte contractility (19,42) and angiogenesis (21,43), but also limiting inflammation (39) and lowering blood pressure (18,44). Although the expression of APJ argues for a direct role of apelin in lymphatic endothelium, all of these effects of apelin on the cardiac microenvironment may indirectly influence the lymphatic function.…”

ELABELA: a novel hormone in cardiac development acting as a new endogenous ligand for the APJ receptor

“…So ELA replacement therapy may also be an effective way to treat heart disease. For example, loss of cardiomyocytes often leads to heart failure, and apelin-13 has been shown to recruit stem cells and induce vascular progenitor cells to home into infarcted mouse hearts after myocardial damage by activating APJ receptor [34,35]. ELA activates APJ and has a function in hESC differentiation, so ELA supplement may be a new way to produce cardiomyocytes and an effective cure for heart failure.…”