Structure and dynamics of the N-terminal half of hepatitis C virus core protein: an intrinsically unstructured protein |
| |
Authors: | Duvignaud Jean-Baptiste Savard Christian Fromentin Rémi Majeau Nathalie Leclerc Denis Gagné Stéphane M |
| |
Institution: | a Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, PR China b Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China |
| |
Abstract: | It has been reported that cyclosporine A (CsA) aggravates vascular injury in hyperlipidemic patients, but the specific mechanisms are unclear. We explored the hypothesis that CsA may result in complement-mediated endothelial cell lysis induced by down-regulation of decay-accelerating factor (DAF) in hyperlipidemic patients. Human umbilical vein endothelial cells (HUVECs) were treated with CsA or/and oxidized low-density lipoprotein (ox-LDL) before allowing DAF expression. Complement factor C3 cell binding was measured by flow cytometry. CsA exposure led to decreased DAF expression and aggravated cell lysis of the HUVECs pre-incubated with ox-LDL, in a dose-dependent fashion. In in vivo experiments using thoracic aortic endothelium from hyperlipidemic rats, CsA resulted in dose-dependent down-regulation of DAF, and accompanying endothelial damage. These observations provide new evidence that hyperlipidemic patients treated with CsA may have an increased vascular risk, at least in part through complement-mediated EC lysis following down-regulated DAF expression. |
| |
Keywords: | Decay-accelerating factor Hyperlipidemia Cyclosporine A Cell lysis Vascular endothelial growth factor |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|