title: Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol.
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.
authors.affiliation: Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia The Ritchie Centre, Monash University, Melbourne, VIC, Australia Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Mandar S
authors.initials: MS
authors.lastname: Joshi
authors.affiliation: Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.affiliation: Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Horlock
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Thilini
authors.initials: T
authors.lastname: Samarasinghe
authors.affiliation: Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Andrews
authors.affiliation: Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Ann-Maree
authors.initials: AM
authors.lastname: Jefferis
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, VIC, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Berger
authors.affiliation: Vascular Pharmacology, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Jaye P
authors.initials: JP
authors.lastname: Chin-Dusting
authors.affiliation: Heart Failure Research Group, Cardiology Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia Heart Failure Unit, Alfred Hospital, Melbourne, VIC, Australia david.kaye@bakeridi.edu.au.
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D000067268:Isolated Heart Preparation; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D013267:Stilbenes; D000077185:Resveratrol
keywords: Diabetes; cardiac dysfunction; microvascular; mitochondria; resveratrol