Cyclosporine A aggravates vascular endothelial injury in hyperlipidemic rats by down-regulating decay-accelerating factor.
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.
Wang
Wei
W
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, PR China.
Zhang
Peng
P
Wang
Jinjing
J
Bu
Hong
H
D000818:Animals; D018958:CD55 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014470:Umbilical Cord / Q000187:drug effects; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D018958:CD55 Antigens; D007166:Immunosuppressive Agents; D042461:Vascular Endothelial Growth Factor A; D016572:Cyclosporine