Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 127, Issue -, Pages 270-276Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2019.01.003
Keywords
-
Categories
Funding
- National Institute of Health
- Foundation Leducq
- Japan Society for the Promotion of Science
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZICHL005904, ZICHL005907, ZIAHL005702] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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 beta-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 (FM) into the mitochondria. Using conditional alleles of these mitochondria] 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available