Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits
High levels of plasma high-density lipoprotein-cholesterol (HDL-C) are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP) is considered to be a therapeutic method of raising HDL-C leve...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/3824276 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832568349164306432 |
|---|---|
| author | Shoucui Gao Xiaojing Wang Daxing Cheng Jiayan Li Lu Li Linwu Ran Sihai Zhao Jianglin Fan Enqi Liu |
| author_facet | Shoucui Gao Xiaojing Wang Daxing Cheng Jiayan Li Lu Li Linwu Ran Sihai Zhao Jianglin Fan Enqi Liu |
| author_sort | Shoucui Gao |
| collection | DOAJ |
| description | High levels of plasma high-density lipoprotein-cholesterol (HDL-C) are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP) is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg) rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells. |
| format | Article |
| id | doaj-art-4242dafdb55d4e05b5d84e3d1f8e9e95 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4242dafdb55d4e05b5d84e3d1f8e9e952025-02-03T00:59:10ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/38242763824276Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic RabbitsShoucui Gao0Xiaojing Wang1Daxing Cheng2Jiayan Li3Lu Li4Linwu Ran5Sihai Zhao6Jianglin Fan7Enqi Liu8Research Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an, Shaanxi 710061, ChinaResearch Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an, Shaanxi 710061, ChinaResearch Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an, Shaanxi 710061, ChinaLaboratory Animal Center, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, ChinaLaboratory Animal Center, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, ChinaLaboratory Animal Center, Ningxia Medical University, Ningxia 750004, ChinaResearch Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an, Shaanxi 710061, ChinaDepartment of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, JapanResearch Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Center, Xi’an, Shaanxi 710061, ChinaHigh levels of plasma high-density lipoprotein-cholesterol (HDL-C) are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP) is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg) rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells.http://dx.doi.org/10.1155/2017/3824276 |
| spellingShingle | Shoucui Gao Xiaojing Wang Daxing Cheng Jiayan Li Lu Li Linwu Ran Sihai Zhao Jianglin Fan Enqi Liu Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits Mediators of Inflammation |
| title | Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits |
| title_full | Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits |
| title_fullStr | Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits |
| title_full_unstemmed | Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits |
| title_short | Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits |
| title_sort | overexpression of cholesteryl ester transfer protein increases macrophage derived foam cell accumulation in atherosclerotic lesions of transgenic rabbits |
| url | http://dx.doi.org/10.1155/2017/3824276 |
| work_keys_str_mv | AT shoucuigao overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT xiaojingwang overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT daxingcheng overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT jiayanli overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT luli overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT linwuran overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT sihaizhao overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT jianglinfan overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits AT enqiliu overexpressionofcholesterylestertransferproteinincreasesmacrophagederivedfoamcellaccumulationinatheroscleroticlesionsoftransgenicrabbits |