Endothelial cells respond to forces generated by laminar blood flow with changes in vasodilation, anticoagulant, fibrinolytic, or anti-inflammatory functions which preserve vessel patency. These responses to flow shear stress are primarily mediated by the modulation of the following transcription factors: Krüppel-like factors 2 and 4 (KLF2 and KLF4). Notably, disturbed flow patterns, which are found in vascular areas predisposed to atherosclerosis, significantly reduce the endothelial expression of KLF2 and KLF4, resulting in changes in the transcriptome that exacerbate inflammation and thrombosis. The endothelial CCM (Cerebral Cavernous Malformation) complex, comprising KRIT1 (Krev1 interaction trapped gene 1), CCM2 (Malcavernin), and CCM3 (Programmed cell death protein 10), suppresses the expression of KLF2 and KLF4. Loss of function of the CCM complex has recently been suggested to protect from coronary atherosclerosis in humans. We thus hypothesized that the silencing of