Apelin-13 Inhibits Methylglyoxal-Induced Unfolded Protein Responses and Endothelial Dysfunction via Regulating AMPK...

Area of Science:

• Cardiovascular Biology
• Metabolic Disease Research
• Cellular Stress Response

Background:

• Methylglyoxal (MGO), a reactive glycolytic byproduct, may contribute more to endothelial dysfunction than high glucose.
• Endoplasmic reticulum (ER) stress and apoptosis are implicated in ischemic heart disease, potentially modulated by apelin.
• Understanding MGO's role in endothelial dysfunction is crucial for cardiovascular health, especially in metabolic conditions.

Purpose of the Study:

• To elucidate the molecular mechanism of MGO-induced endothelial dysfunction mediated by ER stress.
• To evaluate the protective effects of apelin-13 against MGO-induced aortic endothelial dysfunction.
• To investigate the role of the AMPK pathway in apelin-13's protective actions.

Main Methods:

• Assessed MGO-induced ER stress and apoptosis in human umbilical vein endothelial cells (HUVECs) using immunoblotting and MTT assays.
• Evaluated MGO-induced aortic endothelial dysfunction in mouse aortic rings via immunostaining and acetylcholine-induced vasodilation.
• Utilized TUDCA (ER stress inhibitor) and apelin-13 in ex vivo and in vivo models.

Main Results:

• MGO induced ER stress and apoptosis in HUVECs, which was attenuated by the ER stress inhibitor TUDCA.
• Apelin-13 significantly reduced MGO-induced unfolded protein responses (UPR) and aortic endothelial dysfunction.
• Apelin-13 demonstrated protective effects against MGO-induced UPR and endothelial apoptosis via the AMPK pathway.

Conclusions:

• MGO induces endothelial apoptosis and dysfunction primarily through ER stress and UPR activation.
• Apelin-13 effectively mitigates MGO-induced endothelial damage by modulating ER stress and UPR.
• Apelin-13's therapeutic potential in managing diabetic cardiovascular complications warrants further investigation through the AMPK pathway.