دورية أكاديمية
Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis.
| العنوان: | Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis. |
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| المؤلفون: | Wang Y; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada.; Division of Vascular Surgery, Stanford University, CA (Y.W., N.J.L.)., Dubland JA; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Allahverdian S; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Asonye E; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Sahin B; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Jaw JE; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Sin DD; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Seidman MA; Pathology and Laboratory Medicine (M.A.S.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada., Leeper NJ; Division of Vascular Surgery, Stanford University, CA (Y.W., N.J.L.)., Francis GA; From the Departments of Medicine (Y.W., J.A.D., S.A., E.A., B.S., J.E.J., D.D.S., G.A.F.), Centre for Heart Lung Innovation, Providence Healthcare Research Institute, St Paul's Hospital, University of British Columbia, Vancouver, Canada. |
| المصدر: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2019 May; Vol. 39 (5), pp. 876-887. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas, TX : American Heart Association, c1995- |
| مواضيع طبية MeSH: | ATP Binding Cassette Transporter 1/*genetics , Apolipoproteins E/*deficiency , Atherosclerosis/*pathology , Foam Cells/*metabolism , Myocytes, Smooth Muscle/*metabolism, Animals ; Atherosclerosis/metabolism ; Cholesterol/metabolism ; Disease Models, Animal ; Female ; Gene Expression Regulation ; Humans ; Male ; Mice ; Reference Values ; Risk Factors |
| مستخلص: | 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 ≈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. |
| التعليقات: | Comment in: Arterioscler Thromb Vasc Biol. 2019 May;39(5):836-838. (PMID: 31017823) |
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| معلومات مُعتمدة: | R35 HL144475 United States HL NHLBI NIH HHS; S10 RR027431 United States RR NCRR NIH HHS; Canada CAPMC CIHR |
| فهرسة مساهمة: | Keywords: atherosclerosis; cholesterol; foam cells; macrophages; smooth muscle |
| المشرفين على المادة: | 0 (ABCA1 protein, human) 0 (ATP Binding Cassette Transporter 1) 0 (Apolipoproteins E) 97C5T2UQ7J (Cholesterol) |
| تواريخ الأحداث: | Date Created: 20190222 Date Completed: 20200130 Latest Revision: 20200501 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6482082 |
| DOI: | 10.1161/ATVBAHA.119.312434 |
| PMID: | 30786740 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1524-4636 |
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| DOI: | 10.1161/ATVBAHA.119.312434 |