The role of AMP-activated protein kinase in the cardiovascular system

It has recently been recognized that adiponectin protects the vasculature and prevents atherosclerotic change through AMP-activated protein kinase (AMPK) activation, and some of its molecular mechanisms have been clarified. AMPK, which might be a therapeutic target of metabolic abnormality, is a serine-threonine kinase, heterotrimer protein composed of three subunits of α, β and γ. It is activated by an upper kinase LKB1 and an increase in the AMP/ATP ratio. Some anabolic enzymes are directly phosphorylated and inhibited, suggesting that AMPK suppresses ATP consumption by negatively regulating the synthetic pathway. The LKB1–AMPK pathway is pivotal for controlling cellular polarity and mitosis. Furthermore, AMPK has been associated with cellular autophagy. AMPK activation could induce autophagy and prolong a period leading to cell apoptosis. Apoptosis under anoxic conditions was decreased when newly constructed, constitutively active mutants of AMPK-α were overexpressed in vascular endothelial cells. AMPK could inhibit the growth of vascular smooth muscle through MEK–ERK pathway inhibition. After ischemia reperfusion, dominant-negative AMPK overexpression inhibits cardiac function through the suppression of glucose uptake and fatty acid β-oxidation in cardiac myocytes. Cardiac hypertrophy with accumulation of glycogen granules because of gene mutation of γ2 associated with the Wolff-Parkinson-White syndrome has been considered an activated type in most cases. It is necessary to clarify the tissue-specific and stress-specific activation mechanism of AMPK.