Crippling of Krüppel (-Like Factor 2) by Bad Flow Portends a miRky Day for Endothelial Function

Kruppel-like Factor 2 (KLF2) is a 38-kDa transcription factor that is highly expressed in the vascular endothelium. The enormous attention that KLF2 has received in recent years is well deserved, because experimental evidence has shown that it is a vital protein that, via transcriptional and nontranscriptional targets, mediates a host of endothelial functions.1 These include inhibition of vascular inflammation and attendant atherosclerosis, maintenance of an antithrombotic endothelial surface, stimulation of endothelial nitric oxide synthase expression and vascular nitric oxide production, inhibition of hypoxia-stimulated angiogenesis, and promotion of prenatal vasculogenesis, among others. It is not surprising, therefore, that regulation of endothelial KLF2 expression has been the subject of intense investigation.Article see p 633Systole, diastole, and the intrinsic elasticity of the arterial tree results in a blood flow that is pulsatile in fashion. This blood flow, in straight parts of the arterial tree, imparts a laminar stress on the endothelium. Laminar flow stimulates endothelial KLF2 expression.2 Segments of the arterial tree that face pulsatile laminar flow are less prone to the development of atherosclerotic plaque than those that are subject to oscillatory flow (which results in nonlaminar shear), such as at branch points and curvatures.3 Parallel with the susceptibility of arterial regions exposed to oscillatory flow to atheromatous changes, endothelial KLF2 expression is decreased in such regions.2 Consistent with the role of KLF2 in stimulating endothelial nitric oxide synthase expression and nitric oxide production, laminar flow promotes endothelium-dependent vasorelaxation,4,5 whereas oscillatory flow impairs it.6 Differential regulation of endothelial KLF2 expression in response …