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.


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.
Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH 44106-7290, USA. nikunj.sharma@case.edu
Nikunj
N
Sharma
Yuan
Y
Lu
Guangjin
G
Zhou
Xudong
X
Liao
Parul
P
Kapil
Puneet
P
Anand
Ganapati H
GH
Mahabeleshwar
Jonathan S
JS
Stamler
Mukesh K
MK
Jain
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005487:Foam Cells / Q000473:pathology / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D001057:Apolipoproteins E; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors