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. CONCLUSIONS: Our findings identify myeloid KLF4 as an essential regulator of vascular inflammation and experimental atherogenesis.
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-deficientmice (ApoE(-/-) background) develop significantly more vascular inflammation and atherosclerotic lesion formation. CONCLUSIONS: Our findings identify myeloid KLF4 as an essential regulator of vascular inflammation and experimental atherogenesis.
Authors: Anne Hamik; Zhiyong Lin; Ajay Kumar; Mercedes Balcells; Sumita Sinha; Jonathan Katz; Mark W Feinberg; Robert E Gerzsten; Elazer R Edelman; Mukesh K Jain Journal: J Biol Chem Date: 2007-03-05 Impact factor: 5.157
Authors: Xudong Liao; Nikunj Sharma; Fehmida Kapadia; Guangjin Zhou; Yuan Lu; Hong Hong; Kaavya Paruchuri; Ganapati H Mahabeleshwar; Elise Dalmas; Nicolas Venteclef; Chris A Flask; Julian Kim; Bryan W Doreian; Kurt Q Lu; Klaus H Kaestner; Anne Hamik; Karine Clément; Mukesh K Jain Journal: J Clin Invest Date: 2011-06-13 Impact factor: 14.808
Authors: Mark W Feinberg; Akm Khyrul Wara; Zhuoxiao Cao; Maria A Lebedeva; Frank Rosenbauer; Hiromi Iwasaki; Hideyo Hirai; Jonathan P Katz; Richard L Haspel; Susan Gray; Koichi Akashi; Julie Segre; Klaus H Kaestner; Daniel G Tenen; Mukesh K Jain Journal: EMBO J Date: 2007-08-30 Impact factor: 11.598
Authors: Eugene A Podrez; Eugenia Poliakov; Zhongzhou Shen; Renliang Zhang; Yijun Deng; Mingjiang Sun; Paula J Finton; Lian Shan; Bogdan Gugiu; Paul L Fox; Henry F Hoff; Robert G Salomon; Stanley L Hazen Journal: J Biol Chem Date: 2002-07-08 Impact factor: 5.157