Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis[S]

Journal of Lipid Research

卷:53

Stephen J. Demosky¹  Mona Ghias²  John A. Stonik³  Maureen L. Sampson³  Stewart J. Levine³  Cuilian Dai⁴  Alan T. Remaley⁴  Cathy L. Knapper⁴  Boris L. Vaisman⁵ 

[1] Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute;

[2] To whom correspondence should be addressed;

[3] and;

关键词: endothelial cells;    cholesterol efflux;    reverse cholesterol transport;    high density lipoprotein;    ATP binding cassette transporter A1;   

DOI  :  

来源: DOAJ

【 摘 要 】

The role of endothelial ABCA1 expression in reverse cholesterol transport (RCT) was examined in transgenic mice, using the endothelial-specific Tie2 promoter. Human ABCA1 (hABCA1) was significantly expressed in endothelial cells (EC) of most tissues except the liver. Increased expression of ABCA1 was not observed in resident peritoneal macrophages. ApoA-I-mediated cholesterol efflux from aortic EC was 2.6-fold higher (P < 0.0001) for cells from transgenic versus control mice. On normal chow diet, Tie2 hABCA1 transgenic mice had a 25% (P < 0.0001) increase in HDL-cholesterol (HDL-C) and more than a 2-fold increase of eNOS mRNA in the aorta (P < 0.04). After 6 months on a high-fat, high-cholesterol (HFHC) diet, transgenic mice compared with controls had a 40% increase in plasma HDL-C (P < 0.003) and close to 40% decrease in aortic lesions (P < 0.02). Aortas from HFHC-fed transgenic mice also showed gene expression changes consistent with decreased inflammation and apoptosis. Beneficial effects of the ABCA1 transgene on HDL-C levels or on atherosclerosis were absent when the transgene was transferred onto ApoE or Abca1 knockout mice. In summary, expression of hABCA1 in EC appears to play a role in decreasing diet-induced atherosclerosis in mice and is associated with increased plasma HDL-C levels and beneficial gene expression changes in EC.

【 授权许可】

Unknown