Regression and stabilization of advanced murine atherosclerotic lesions: a comparison of LDL lowering and HDL raising gene transfer strategies.
Regression and stabilization of advanced murine atherosclerotic lesions: a comparison of LDL lowering and HDL raising gene transfer strategies.
复制标题
晚期小鼠动脉粥样硬化病变的消退和稳定：降低 LDL 和提高 HDL 基因转移策略的比较。
DOI：
10.1007/s00109-011-0722-x
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发表时间：
2011-06
影响因子：
4.7
通讯作者：
De Geest, Bart
中科院分区：
文献类型：
--
作者：
Van Craeyveld, Eline;Gordts, Stephanie C.;Nefyodova, Elena;Jacobs, Frank;De Geest, Bart
关键词：
Both reductions in atherogenic lipoproteins and increases in high-density lipoprotein (HDL) levels may affect atherosclerosis regression. Here, the relative potential of low-density lipoprotein (LDL) lowering and HDL raising gene transfer strategies to induce regression of complex murine atherosclerotic lesions was directly compared. Male C57BL/6 LDL receptor (LDLr)−/− mice were fed an atherogenic diet (1.25% cholesterol and 10% coconut oil) to induce advanced atherosclerotic lesions. A baseline group was killed after 6 months and remaining mice were randomized into a control progression (Adnull or saline), an apolipoprotein (apo) A-I (AdA-I), an LDLr (AdLDLr), or a combined apo A-I/LDLr (AdA-I/AdLDLr) adenoviral gene transfer group and followed-up for another 12 weeks with continuation of the atherogenic diet. Gene transfer with AdLDLr decreased non-HDL cholesterol levels persistently by 95% (p < 0.001) compared with baseline. This drastic reduction of non-HDL cholesterol levels induced lesion regression by 28% (p < 0.001) in the aortic root and by 25% (p < 0.05) in the brachiocephalic artery at 12 weeks after transfer. Change in lesion size was accompanied by enhanced plaque stability, as evidenced by increased collagen content, reduced lesional macrophage content, a drastic reduction of necrotic core area, and decreased expression of inflammatory genes. Elevated HDL cholesterol following AdA-I transfer increased collagen content in lesions, but did not induce regression. Apo A-I gene transfer on top of AdLDLr transfer resulted in additive effects, particularly on inflammatory gene expression. In conclusion, drastic lipid lowering induced by a powerful gene transfer strategy leads to pronounced regression and stabilization of advanced murine atherosclerosis. The online version of this article (doi:10.1007/s00109-011-0722-x) contains supplementary material, which is available to authorized users.
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影响因子：
120.7
作者：
Nicholls, Stephen J.;Tuzcu, E. Murat;Nissen, Steven E.
通讯作者：
Nissen, Steven E.
影响因子：
15.9
作者：
Seo, T;Qi, KM;Deckelbaum, RJ
通讯作者：
Deckelbaum, RJ
影响因子：
8.7
作者：
Dhore, CR;Cleutjens, JPM;Daemen, MJAP
通讯作者：
Daemen, MJAP
影响因子：
37.8
作者：
Tangirala, RK;Tsukamoto, K;Rader, DJ
通讯作者：
Rader, DJ
DOI：
10.1161/atvbaha.108.176644
发表时间：
2009-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Manning-Tobin JJ;Moore KJ;Seimon TA;Bell SA;Sharuk M;Alvarez-Leite JI;de Winther MP;Tabas I;Freeman MW
通讯作者：
Freeman MW