Apelin/APJ relieve diabetic cardiomyopathy by reducing microvascular dysfunction

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Molecular Medicine

Background:

• Diabetic cardiomyopathy is linked to microcirculatory injuries, primarily endothelial cell dysfunction.
• Apelin, an adipokine elevated in diabetes, shows potential in improving endothelial function and mitigating cardiac issues.

Purpose of the Study:

• To investigate the role of apelin in alleviating endothelial cell dysfunction and subsequent diabetic cardiomyopathy.
• To elucidate the molecular mechanisms underlying apelin's effects on endothelial cells in diabetes.

Main Methods:

• Assessed apelin's impact on endothelial cell apoptosis, proliferation, angiogenesis, and adhesion molecule expression.
• Utilized endothelial cell-specific APJ knockout mice and in vitro cell cultures.
• Investigated the involvement of APJ receptor and NFκB pathways.

Main Results:

• Apelin treatment enhanced endothelial cell proliferation, angiogenesis, and E-cadherin/VEGFR 2/Tie-2 expression while decreasing apoptosis and adhesion molecules.
• Apelin reduced cardiac microvascular permeability and attenuated diabetic cardiomyopathy.
• Apelin's beneficial effects on endothelial cells were confirmed to be APJ-dependent and involve NFκB signaling.

Conclusions:

• Apelin ameliorates endothelial dysfunction in diabetic cardiomyopathy by improving endothelial cell function and integrity.
• The protective effects of apelin are mediated through the APJ receptor and downstream NFκB pathways.
• Apelin represents a promising therapeutic target for managing diabetic microvascular complications and cardiomyopathy.