The Effect of Mangiferin on Improving Endothelial Dysfunction by Inhibiting Endoplasmic Reticulum Stress to Alleviate Mitochondrial Fission

Yang Chen

doi:10.11648/j.ajcem.20170505.12

Abstract

Microvascular and macrovascular diseases are important complications of metabolic diseases and affect the normal functioning of the human cardiovascular system. Endothelial dysfunction is the basic pathological tache of vascular diseases. This study aims to find out whether mangiferin can relieve endothelial dysfunction by inhibiting mitochondrial fission induced by endoplasmic reticulum stress. After being stimulated by palmitate, the expression of endoplasmic reticulum stress-related proteins Bip, p-PERK (RNA-like endoplasmic reticulum kinase) increased significantly. The endoplasmic reticulum stress was effectively inhibited after the treatment with mangiferin and the inhibition diminished after the knockout of AMPK (AMP-activated protein kinase) through AMPK siRNA interference, which demonstrated that AMPK was a key point for mangiferin action to exert its therapeutic effects. Under endoplasmic reticulum stress conditions, the influx of calcium ions from the endoplasmic reticulum into cytoplasm may lead to mitochondrial calcium ions overload and a large increase in mitochondrial ROS. As a result, mitochondrial fission was further promoted and apoptosis was induced. Mangiferin effectively improved the endothelial function by activating AMPK to inhibit the endoplasmic reticulum stress, maintaining the calcium homeostasis in mitochondria while inhibiting apoptosis by diminishing mitochondrial fission and ROS (Reactive Oxygen Specie) generation. In conclusion, mangiferin could maintain Ca2+ homeostasis in mitochondria under ER stress conditions, attenuate cell apoptosis induced by mitochondrial fission and ROS generation, and effectively improve the endothelial function by activating AMPK to inhibit endoplasmic reticulum stress.

Highlights

Obesity and diabetes are accompanied with an increasing risk of developing cardiovascular disease[1,2,3,4], since glucose and lipid metabolism disorder can stimulate vascular endothelial cells to induce a stress response, to which endoplasmic reticulum (ER) and mitochondria are exquisitely sensitive [2,3,4,5]
The results demonstrated that MGF could improve endothelial dysfunction by attenuating [Ca2+]mito overload-induced mitochondrial fission and inhibiting mitochondrial ROS production to depress ER stress and maintain ER homeostasis through activating AMPK pathway
A variety of studies have demonstrated that ER stress and unfolded protein response (UPR) are associated with chronic metabolic disease and cardiovascular disease [29, 30]

Summary

Introduction

Obesity and diabetes are accompanied with an increasing risk of developing cardiovascular disease[1,2,3,4], since glucose and lipid metabolism disorder can stimulate vascular endothelial cells to induce a stress response, to which endoplasmic reticulum (ER) and mitochondria are exquisitely sensitive [2,3,4,5]. If such an external stimulation is prolonged, endoplasmic cells cannot maintain the normal physiological functions by self-regulation and pathological stress occurs as a result.

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Conclusion