首页 | 本学科首页   官方微博 | 高级检索  
   检索      


α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol
Authors:Rami Abu-Fanne  Emad Maraga  Ihab Abd-Elrahman  Aviel Hankin  Galia Blum  Suhair Abdeen  Nuha Hijazi  Douglas B Cines  Abd Al-Roof Higazi
Institution:From the Department of Clinical Biochemistry and ;the §School of Pharmacy, Hadassah-Hebrew University, Jerusalem IL-91120, Israel and ;the Department of Pathology and Laboratory Medicine, Perelman School of Medicine-University of Pennsylvania, Philadelphia, Pennsylvania 19104
Abstract:Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil α-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human α-defensins in their polymorphonuclear leukocytes (Def+/+). Accelerated Def+/+ mice developed α-defensin·LDL complexes that accelerate the clearance of LDL from the circulation accompanied by enhanced vascular deposition and retention of LDL, induction of endothelial cathepsins, increased endothelial permeability to LDL, and the development of lipid streaks in the aortic roots when fed a regular diet and at normal plasma levels of LDL. Transplantation of bone marrow from Def+/+ to WT mice increased LDL clearance, increased vascular permeability, and increased vascular deposition of LDL, whereas transplantation of WT bone marrow to Def+/+ mice prevented these outcomes. The same outcome was obtained by treating Def+/+ mice with colchicine to inhibit the release of α-defensins. These studies identify a potential new link between inflammation and the development of atherosclerosis.
Keywords:atherosclerosis  defensin  lipoprotein  low density lipoprotein (LDL)  neutrophil  α  -defensins  atherosclerosis
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号