Protective effects of AMP-activated protein kinase in the cardiovascular system

Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide. Recent studies of AMP-activated protein kinase (AMPK), a highly conserved sensor of cellular energy status, suggest that there might be therapeutic value in targeting the AMPK signaling pathway. AMPK is found in most mammalian tissues, including those of the cardiovascular system. As cardiovascular diseases are typically associated with blood flow occlusion and blood occlusion may induce rapid energy deficit, AMPK activation may occur during the early phase upon nutrient deprivation in cardiovascular organs. Therefore, investigation of AMPK in cardiovascular organs may help us to understand the pathophysiology of defence mechanisms in these organs. Recent studies have provided proof of concept for the idea that AMPK is protective in heart as well as in vascular endothelial and smooth muscle cells. Moreover, dysfunction of the AMPK signalling pathway is involved in the genesis and development of various cardiovascular diseases, including atherosclerosis, hypertension and stroke. The roles of AMPK in the cardiovascular system, as they are currently understood, will be presented in this review. The interaction between AMPK and other cardiovascular signalling pathways such as nitric oxide signalling is also discussed.

Fig 1

Proposed model illustrating protein factors upstream and downstream of AMPK (refer to text for additional detail). Upper arrows show kinase-mediated activation of AMPK via Ca²⁺/calmodulin-dependent protein kinase β (CaMKKβ), LKB1 and TGFβ-activated kinase (TAK1). Lower arrows indicate targets of AMPK, including endothelial nitric oxide synthase (eNOS), acetyl-CoA carboxylase (ACC), glucose transporter type 4 (GLUT4) and 6-phosphofructo-1-kinase (PFK1).