Kruppel-like factors (KLFs) are members of the zinc-finger transcription factors family that are critical in the regulation of cell proliferation, differentiation and inflammation1, 2. So far, the mammalian KLF family has 17 members3, each has 3 contiguous C2H2 (cysteine-histidine) type zinc fingers at the carboxyl terminus4, 5. In particular, KLF2 can modulate expression of genes critical in regulating endothelial homeostasis, vascular tone, thrombosis and inflammation, and has been regarded as an atheroprotective factor2, 6, 7. KLF2 is potently induced by laminar shear stress and confers anti-inflammatory and anti-thrombotic effects on the endothelium7, 8. KLF2 strongly induces endothelial nitric oxide synthase (eNOS) expression, but decreased vascular cell adhesion molecule 1 (VCAM1) and endothelin-1 (ET-1) expression4, 9–11. Endothelial KLF2 expression is regulated by the MEK5/ERK5 (dual specificity mitogen-activated protein kinase 5 (MEK5)/extracellular-signal related kinase 5 (ERK5) pathway requiring myocyte enhancer factor 2 (MEF2) transcription factor, which mediates beneficial effects of laminar flow12–14. Our previous studies showed that KLF2 was also negatively regulated by histone deacetylase 5 (HDAC5)15, 16. In vivo animal experiments demonstrated that endothelial cell-specific deficiency of KLF2 predisposed to atherosclerosis development17. Hemizygous deficiency in Klf2+/−mice on apolipoprotein E deficient (ApoE −/−) background (Klf2 +/−; ApoE −/−) exhibited increased diet-induced atherosclerosis versus wild-type ApoE deficient mice (Klf2 +/+; ApoE −/−)2. In addition, myeloid-specific Klf2 knockout in an atheroprone LDL receptor-deficient background (Ldl −/−) increased atherosclerosis progression18.