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Publication : Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis.

First Author  Wang Y Year  2019
Journal  Arterioscler Thromb Vasc Biol Volume  39
Issue  5 Pages  876-887
PubMed ID  30786740 Mgi Jnum  J:291389
Mgi Id  MGI:6443948 Doi  10.1161/ATVBAHA.119.312434
Citation  Wang Y, et al. (2019) Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis. Arterioscler Thromb Vasc Biol 39(5):876-887
abstractText  Objective- Smooth muscle cells (SMCs) are the most abundant cells in human atherosclerotic lesions and are suggested to contribute at least 50% of atheroma foam cells. In mice, SMCs contribute fewer total lesional cells. The purpose of this study was to determine the contribution of SMCs to total foam cells in apolipoprotein E-deficient (ApoE(-/-)) mice, and the utility of these mice to model human SMC foam cell biology and interventions. Approach and Results- Using flow cytometry, foam cells in the aortic arch of ApoE(-/-) mice were characterized based on the expression of leukocyte-specific markers. Nonleukocyte foam cells increased from 37% of total foam cells in 27-week-old to 75% in 57-week-old male ApoE(-/-) mice fed a chow diet and were approximately 70% in male and female ApoE(-/-) mice following 6 weeks of Western diet feeding. A similar contribution to total foam cells by SMCs was found using SMC-lineage tracing ApoE(-/-) mice fed the Western diet for 6 or 12 weeks. Nonleukocyte foam cells contributed a similar percentage of total atheroma cholesterol and exhibited lower expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1) when compared with leukocyte-derived foam cells. Conclusions- Consistent with previous studies of human atheromas, we present evidence that SMCs contribute the majority of atheroma foam cells in ApoE(-/-) mice fed a Western diet and a chow diet for longer periods. Reduced expression of ABCA1, also seen in human intimal SMCs, suggests a common mechanism for formation of SMC foam cells across species, and represents a novel target to enhance atherosclerosis regression.
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