Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes.
The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced CAD. Endothelium-dependent vasodilation was impaired in patients with CAD and T2D relative to those with CAD alone. Levels of mitochondrial H(2)O(2) and activity of AMPK were significantly elevated in primary HSVECs (human saphenous vein endothelial cells) from patients with CAD and T2D compared with those from patients with CAD alone. Incubation with the mitochondria-targeted antioxidant, MitoQ(10) significantly reduced AMPK activity in HSVECs from patients with CAD and T2D but not in cells from patients with CAD alone. Elevated mtROS production in the endothelium of patients with CAD and T2D increases AMPK activation, supporting a role for the kinase in defence against oxidative stress. Further investigation is required to determine whether pharmacological activators of AMPK will prove beneficial in the attenuation of endothelial dysfunction in patients with CAD and T2D.
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Ruth M
RM
Mackenzie
Ian P
IP
Salt
William H
WH
Miller
Angela
A
Logan
Hagar A
HA
Ibrahim
Andrea
A
Degasperi
Jane A
JA
Dymott
Carlene A
CA
Hamilton
Michael P
MP
Murphy
Christian
C
Delles
Anna F
AF
Dominiczak
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000368:Aged; D003324:Coronary Artery Disease / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases