Regulation of endothelial cell metabolism: just go with the flow.

T he vascular endothelium, the major interface of the vessel wall between blood and all tissues, must constantly adapt to fluctuations in environmental cues. Cellular metabolism is one mechanism that may contribute to rapid dynamic changes in cell phenotype. For example, glycolysis, one of the major forms of cellular metabolism that converts glucose to pyruvate, is required for immune cell activation, tumor cell proliferation and survival, and the phenotypic switch of endo-thelial cells (ECs) between quiescent and angiogenic states. 1–8 ECs are exposed to a variety of stimuli, such as turbulent/ disturbed shear stress and hypoxia under pathophysiological states. To maintain homeostatic control of ECs, gene expression in ECs is subjected to highly tight regulation at multiple levels, including transcriptional and epigenetic control. Exposure of vascular ECs to atheroprotective laminar shear stress promotes anti-inflammatory, antithrombotic, and anti-oxidative properties largely through inducing the expression of a cassette of transcriptional regulators, including Kruppel-like factor-2 (KLF2). 9 Biomechanical stimuli also contribute to a resting quiescent state in ECs. 10 However, the underlying mechanisms by which biomechanical stimuli, such as laminar shear stress, regulate cellular metabolism, including glycoly-sis and mitochondrial content, to maintain this resting metabolic state in ECs remains poorly understood. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Doddaballapur et al 11 present elegant studies addressing the role of laminar shear stress in cellular metabolism of ECs. They report that laminar shear stress reduced EC glycol-ysis by regulating the expression of KLF2 and