Induction of decay accelerating factor and membrane cofactor protein by resveratrol attenuates complement deposition in human coronary artery endothelial cells

被引:3
作者
Detsika, Maria G. [1 ]
Myrtsi, Eleni D. [2 ]
Koulocheri, Sofia D. [2 ]
Haroutounian, Serkos A. [2 ]
Lianos, Elias A. [1 ,3 ,4 ]
Roussos, Charis [1 ]
机构
[1] Natl & Kapodistrian Univ Athens, Evangelismos Hosp, Thorax Fdn, Sch Med,Dept Crit Care Med & Pulm Serv 1,Res Ctr, Athens, Greece
[2] Agr Univ Athens, Dept Nutr Physiol & Feeding, Iera Odos 75, GR-11855 Athens, Greece
[3] Vet Affairs Med Ctr, 1970 Roanoke Blvd, Salem, VA 24153 USA
[4] Virginia Tech, Carilion Sch Med, 1970 Roanoke Blvd, Salem, VA 24153 USA
关键词
D O I
10.1016/j.bbrep.2019.100652
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The involvement of complement activation in various forms of cardiovascular disease renders it an important factor for disease progression and therapeutic intervention. The protective effect of resveratrol against cardiovascular disease via moderate red wine consumption has been established but the exact mechanisms are still under investigation. The current study utilised human coronary artery endothelial cells (HCAECs) in order to assess the extent to which the protective effect of resveratrol, at concentrations present in red wine, can be attributed to the upregulation of complement regulatory proteins through heme-oxygenase (HO)-1 induction. Resveratrol at concentrations as low as 0.001 mu M increased HO-1 expression as well as membrane cofactor protein (MCP, CD46) and decay-accelerating factor (DAF, CD55) expression with no-effect on CD59. Silencing of HO-1 expression by HO-1 siRNAs abrogated both DAF and MCP protein expression with no effect on CD59. Resveratrol-mediated induction of DAF and MCP reduced C3b deposition following incubation of HCAECs with 10% normal human serum or normal rat serum as a source of complement. Incubation of HCAECs, with either a DAF blocking antibody or following transfection with HO-1 siRNAs, in the presence of 10% normal rat serum increased C3b deposition, indicating that both DAF and HO-1 are required for C3b reduction. These observations support a novel mechanism for the protective effect of resveratrol against cardiovascular disease and confirm the important role of HO-1 in the regulation of the complement cascade.
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页数:7
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