Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol

Author:

Joshi Mandar S123,Williams David1,Horlock Duncan1,Samarasinghe Thilini2,Andrews Karen L4,Jefferis Ann-Maree4,Berger Philip J2,Chin-Dusting Jaye P4,Kaye David M15

Affiliation:

1. Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

2. The Ritchie Centre, Monash University, Melbourne, VIC, Australia

3. Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, USA

4. Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

5. Heart Failure Unit, Alfred Hospital, Melbourne, VIC, Australia

Abstract

Microvascular complications are now recognized to play a major role in diabetic complications, and understanding the mechanisms is critical. Endothelial dysfunction occurs early in the course of the development of complications; the precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur in a diabetic rat heart and may act as a source of the oxidative stress. However, the role of endothelial cell-specific mitochondrial dysfunction in diabetic vascular complications is poorly studied. Here, we studied the role of diabetes-induced abnormal endothelial mitochondrial function and the resultant endothelial dysfunction. Understanding the role of endothelial mitochondrial dysfunction in diabetic vasculature is critical in order to develop new therapies. We demonstrate that hyperglycaemia leads to mitochondrial dysfunction in microvascular endothelial cells, and that mitochondrial inhibition induces endothelial dysfunction. Additionally, we show that resveratrol acts as a protective agent; resveratrol-mediated mitochondrial protection may be used to prevent long-term diabetic cardiovascular complications.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Endocrinology, Diabetes and Metabolism,Internal Medicine

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