Sports or statins for atheroprotection? New insight from Kruppel-like factor 2.

Nitric oxide (NO) plays a central role in the control of vascular homeostasis. Adequate NO production stimulated by continuous laminar flow on the endothelial surface, so-called shear stress, prevents endothelial inflammation and development of endothelial dysfunction. Recently, a novel class of mechanosensitive transcription factors has been identified that in endothelial cells transfer shear stress to various downstream targets such as the endothelial NO synthase (eNOS) [1]. These Kruppel-like factors (KLFs) are zinc finger transcription factors that act as transcriptional activators or suppressors upon binding to a CACCC promoter/enhancer element. A total of 16 KLF family members have been identified thus far, but only some are expressed in vascular cells, including KLF2 (reviewed in [2]). In the past, KLF2 was identified as a regulator of T cell differentiation and activation [3]. Recently, shear stress was shown to affect endothelial KLF2 expression with up-regulation by laminar and repression by perturbed flow [4]. KLF2 induces eNOS expression, thereby contributing to the regulation of vascular tone [1]. Interestingly, the up-regulation of eNOS by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is also mediated by KLF2 [5].