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Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits
| Content Provider | Scilit |
|---|---|
| Author | Zhang, Jifeng Niimi, Manabu Yang, Dongshan Liang, Jingyan Xu, Jie Kimura, Tokuhide Mathew, Anna V. Guo, Yanhong Fan, Yanbo Zhu, Tianqing Song, Jun Ackermann, Rose Koike, Yui Schwendeman, Anna Lai, Liangxue Pennathur, Subramaniam Garcia-Barrio, Minerva Fan, Jianglin Chen, Y. Eugene |
| Copyright Year | 2017 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective— CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. Approach and Results— We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet–induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only had higher HDL cholesterol levels but also lower total cholesterol levels than WT rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total cholesterol in KO rabbits was attributable to decreased apolipoprotein B–containing particles, while HDLs remained higher than that in WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. Apolipoprotein B–depleted plasma isolated from CETP KO rabbits showed significantly higher capacity for cholesterol efflux from macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO rabbits suppressed tumor necrosis factor-α–induced vascular cell adhesion molecule 1 and E-selectin expression in cultured endothelial cells. Conclusions— These results provide evidence that genetic ablation of CETP activity protects against cholesterol diet–induced atherosclerosis in rabbits. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805397/pdf https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.117.309114 |
| Ending Page | 1075 |
| Page Count | 8 |
| Starting Page | 1068 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.117.309114 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 6 |
| Volume Number | 37 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2017-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Peripheral Vascular Disease Cholesterol Reduction High-density Lipoprotein Cholesteryl Ester Transfer Protein Genetics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
