AMPK and vasculoprotection.
AMP-activated protein kinase (AMPK) is proposed to be a key regulator of cellular and organismal metabolism and has reported vasculoprotective effects. In addition, many therapeutic agents used in the treatment of diabetes and atherosclerosis such as metformin, thiazolidinediones and statins may exert their vasculoprotective effects through activation of AMPK. Activation of AMPK has a number of potentially beneficial anti-atherosclerotic effects including reducing adhesion of inflammatory cells to the blood vessel endothelium, reducing lipid accumulation and the proliferation of inflammatory cells caused by oxidised lipids, stimulation of gene expression responsible for cellular antioxidant defenses and stimulation of enzymes responsible for nitric oxide formation. In humans and animals the AMPK cascade triggers vascular protective mechanisms that have been shown to reduce myocardial ischaemic injury and mutations in AMPK can cause familial hypertrophic cardiomyopathy. Taken together, these data suggest that activation and function of AMPK contributes to cardiovascular health. In this review we propose to focus on the vasculoprotective effects of AMPK, the evidence for AMPK activation with currently used therapeutic agents and the potential for agents which specifically activate AMPK as a treatment for vascular disease.
College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom.
Marie-Ann
MA
Ewart
Simon
S
Kennedy
D055372:AMP-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D014652:Vascular Diseases / Q000378:metabolism / Q000517:prevention & control*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D045162:Thiazolidinediones; D008687:Metformin; D055372:AMP-Activated Protein Kinases