Myeloid Kruppel-Like Factor 4 Deficiency Augments Atherogenesis in ApoE-/- Mice-Brief Report

Objective-To investigate the role of Kruppel-like factor 4 (KLF4), an essential transcriptional regulator of macrophage polarization (M1/M2), in the pathogenesis of atherosclerosis. Methods and Results-Despite the acknowledged importance of macrophages in atherosclerosis, the role of M1 (classically activated or proinflammatory) versus M2 (alternatively activated or anti-inflammatory) macrophages in this process remains incompletely understood. We recently identified KLF4 as a regulator of macrophage subset specification; that is, KLF4 promotes M2 and inhibits M1 phenotype. Here, we provide evidence that KLF4-deficient macrophages exhibit enhanced proinflammatory activation and foam cell formation in response to oxidized lipids. In vivo, myeloid KLF4-deficient mice (ApoE(-/-) background) develop significantly more vascular inflammation and atherosclerotic lesion formation. Conclusion-Our findings identify myeloid KLF4 as an essential regulator of vascular inflammation and experimental atherogenesis. (Arterioscler Thromb Vasc Biol. 2012;32:2836-2838.)