Macrophage fatty acid oxidation inhibits atherosclerosis progression

Mitsunori Nomura, Jie Liu, Zu Xi Yu, Tomoko Yamazaki, Ye Yan, Hiroyuki Kawagishi, Ilsa I. Rovira, Chengyu Liu, Michael J. Wolfgang, Yoh suke Mukouyama, Toren Finkel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Atherosclerosis is a chronic disorder of the vessel wall. One key regulator of disease progression is lipid handling in macrophages. However, the role of macrophage mitochondrial-dependent fatty acid β-oxidation (FAO) in atherosclerosis is not well defined. To address this, we focused on carnitine palmitoyltransferase (CPT) 1 and 2, which play an essential role in the transport of long chain fatty acids (FAs) into the mitochondria. Using conditional alleles of these mitochondrial enzymes, we have generated myeloid-specific Cpt1a and Cpt2 knockout mutants (CPT1a M-KO and CPT2 M-KO). In culture, macrophages derived from CPT1a and CPT2 M-KO mice have impaired FAO, enhanced expression of the CD36 scavenger receptor, increased uptake of oxidized low-density lipoprotein (oxLDL), and augmented transformation into cholesterol-rich foam cells. In line with these in vitro observations, in the atherosclerosis-susceptible apolipoprotein E (ApoE) KO background, CPT2 M-KO mice demonstrated augmented atherosclerosis, accompanied by increased accumulation of aortic macrophages with elevated CD36 expression. These data suggest that macrophage FAO is athero-protective and that augmenting FAO may potentially slow atherosclerotic progression.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
StatePublished - Feb 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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