title: AMP-activated protein kinase and the control of smooth muscle cell hyperproliferation in vascular disease.
abstract: Smooth muscle cell (SMC) accumulation within the arterial intima contributes to the formation of atherosclerotic lesions. Emerging data indicate that the adenosine monophosphate-activated protein kinase (AMPK) is a potent inhibitor of SMC proliferation. The anti-proliferative action of AMPK is mediated through multiple mechanisms, including the regulation of cyclin dependent kinase inhibitors expression p21(Cip1) and p27(kip1) and the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). A favorable effect of AMPK activation on intima hyperplasia has been demonstrated in in vivo experimental models by using the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), or by studying the AMPKα(-/-) mice. Starting from these evidences, a number of atheroprotective drugs with antiproliferative properties have been shown to induce AMPK phosphorylation. Among them, the Ca(2+) channel blocker nifedipine was demonstrated to act through AMPK, independent of its calcium channel blocking activity. In the present review I summarize current knowledge on the basic biological function of AMPK in relationship to vascular SMC proliferation; the evidence for the role of AMPK in in vivo intima hyperplasia; and the drugs for which a pharmacological activity on AMPK has been shown.
authors.affiliation: Department of Pharmacological Sciences, Via Balzaretti 9, 20133, Milan, Italy. nicola.ferri@unimi.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferri
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D014652:Vascular Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: D055372:AMP-Activated Protein Kinases