Shear Stress-Induced AMP-Activated Protein Kinase Modulation in Endothelial Cells: Its Role in Metabolic Adaptions and Cardiovascular Disease

Abstract

Endothelial cells (ECs) line the inner surface of all blood vessels and form a barrier that facilitates the controlled transfer of nutrients and oxygen from the circulatory system to surrounding tissues. Exposed to both laminar and turbulent blood flow, ECs are continuously subject to differential mechanical stimulation. It has been well established that the shear stress associated with laminar flow (LF) is atheroprotective, while shear stress in areas with turbulent flow (TF) correlates with EC dysfunction. Moreover, ECs show metabolic adaptions to physiological changes, such as metabolic shifts from quiescence to a proliferative state during angiogenesis. The AMP-activated protein kinase (AMPK) is at the center of these phenomena. AMPK has a central role as a metabolic sensor in several cell types. Moreover, in ECs, AMPK is mechanosensitive, linking mechanosensation with metabolic adaptions. Finally, recent studies indicate that AMPK dysregulation is at the center of cardiovascular disease (CVD) and that pharmacological targeting of AMPK is a promising and novel strategy to treat CVDs such as atherosclerosis or ischemic injury. In this review, we summarize the current knowledge relevant to this topic, with a focus on shear stress-induced AMPK modulation and its consequences for vascular health and disease.