Myeloid Krüppel-Like Factor 4 Deficiency Augments Atherogenesis in ApoE−/− Mice—Brief Report
Objective—To investigate the role of Krüppel-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.
- Received April 16, 2012.
- Accepted September 26, 2012.
- © 2012 American Heart Association, Inc.