PPARgamma1-induced caveolin-1 enhances cholesterol efflux and attenuates atherosclerosis in apolipoprotein E-deficient mice.
OBJECTIVE
Caveolin-1 (Cav-1) may positively or negatively influence the development of atherosclerosis, depending on the cell type and the metabolic pathways regulated by this protein. We investigate the effects of Cav-1 on cholesterol efflux in RAW264.7 infected with AdPPARgamma1 and whether Cav-1 could attenuate established atherosclerotic lesions in PPARgamma1-treated apoE-deficient mice.


RESULTS
Compared with AdGFP control, PPARgamma1 and Cav-1 were constitutively overexpressed in AdPPARgamma1-infected RAW264.7 cells, which stimulated cholesterol efflux to apolipoprotein A-I. Using a small interfering RNA approach (Cav-1-siRNA) we achieved an efficient and specific knockdown of caveolin-1 expression (80%), which resulted in a remarkable reduction of cholesterol efflux in RAW264.7 cells . Moreover, PPARgamma1-treated Cav-1-siRNA RAW264.7 cells showed more ability to stimulate cholesterol efflux than Cav-1-siRNA RAW264.7 cells, but far less than control-siRNA RAW264.7 cells and PPARgamma1-treated RAW264.7 cells. In addition, 40-week-old apoE-deficient mice fed a Western-type diet and infected for 4 weeks with AdPPARgamma1 showed induced Cav-1 expression in aortic vascular endothelial cells, smooth muscle cells and macrophages, as well as attenuated established atherosclerotic lesions.


CONCLUSIONS
PPARgamma1 gene therapy could induce Cav-1 expression and enhance cholesterol efflux and attenuate atherosclerosis in apoE-deficient mice.
Hu
Qin
Q
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, China.
Zhang
Xian-Jun
XJ
Liu
Chun-Xi
CX
Wang
Xu-Ping
XP
Zhang
Yun
Y
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D001692:Biological Transport; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014161:Transduction, Genetic; D015854:Up-Regulation
D001057:Apolipoproteins E; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D008074:Lipoproteins; D047495:PPAR gamma; D002784:Cholesterol