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Updated: May 17, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Myeloid Krüppel-like factor 4 deficiency augments atherogenesis in ApoE-/- mice--brief report
Nikunj Sharma1, Yuan Lu, Guangjin Zhou
1Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH 44106-7290, USA. nikunj.sharma@case.edu
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.
Insights
Krüppel-like factor 4 (KLF4) regulates macrophage polarization, impacting atherosclerosis. KLF4 deficiency enhances vascular inflammation and lesion formation, identifying it as a key factor in the disease.
Area of Science:
- Immunology
- Cardiovascular Biology
- Molecular Biology
Background:
- Macrophages play a critical role in atherosclerosis.
- The distinct roles of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages in atherosclerosis are not fully understood.
- Krüppel-like factor 4 (KLF4) has been identified as a regulator of macrophage polarization, promoting M2 and inhibiting M1 phenotypes.
Purpose of the Study:
- To investigate the role of Krüppel-like factor 4 (KLF4) in the pathogenesis of atherosclerosis.
- To determine how KLF4 influences macrophage polarization in the context of atherosclerosis.
Main Methods:
- Investigated KLF4-deficient macrophages in vitro.
- Examined the effects of oxidized lipids on KLF4-deficient macrophages.
- Utilized myeloid KLF4-deficient mice on an ApoE(-/-) background for in vivo studies.
Main Results:
- KLF4-deficient macrophages showed increased proinflammatory activation and foam cell formation upon exposure to oxidized lipids.
- Myeloid KLF4-deficient mice exhibited significantly elevated vascular inflammation.
- Atherosclerotic lesion formation was markedly increased in KLF4-deficient mice.
Conclusions:
- Myeloid KLF4 is a crucial regulator of vascular inflammation.
- KLF4 plays an essential role in experimental atherogenesis.
