AMP-activated protein kinase: a stress-responsive kinase with implications for cardiovascular disease

Abstract

AMP-activated protein kinase (AMPK) was initially viewed as energy sensor and activated by increased intracellular concentrations of AMP following nutrient deprivation. Physiological or pathological stimuli that deplete cellular energy activate AMPK that coordinates a cellular program that limits further ATP depletion and promotes compensatory changes that maintain cellular ATP levels. Recent studies revealed novel roles of AMPK independent of energy status, thereby increasing our understanding of multi-functional roles of AMPK in cells important in pathogenesis of cardiovascular diseases. This enzyme represents an attractive therapeutic target for vascular disease treatment in the future.

Keywords: AMPK; cardiovascular disease; stress.

Figure

Schematic mechanisms for AMPK implication in cardiovascular disease. AMPK is activated by a number of stimuli and its downstream actions have implications for cardiovascular disease. Its effects are pleiotropic in that some pathways are stimulated and others are inhibited. CO, carbon monoxide; AICAR, 5-Aminoimidazole-4-carboxamide riboside; UCP-2, uncoupling protein-2; GTPCH I, GTP-cyclohydrolase I; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; PGC-1α, peroxisome proliferator gamma coactivator-1α; SMC, smooth muscle cell; GLUT4, glucose transporter 4; PFK-2, 6-phosphofructo-2-kinase; ATP, adenosine triphosphate; ACC, acetyl-CoA carboxylase; CPT-1, carnitine palmitoyltransferase-1.