Τίτλος:
Induction of decay accelerating factor and membrane cofactor protein by resveratrol attenuates complement deposition in human coronary artery endothelial cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 μΜ 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. © 2019 The Authors
Συγγραφείς:
Detsika, M.G.
Myrtsi, E.D.
Koulocheri, S.D.
Haroutounian, S.A.
Lianos, E.A.
Roussos, C.
Περιοδικό:
Biochemistry and Biophysics Reports
Λέξεις-κλειδιά:
blocking antibody; complement component C3b; decay accelerating factor; heme oxygenase 1; membrane cofactor protein; protein antibody; regulator protein; resveratrol; small interfering RNA, artery endothelium; Article; cardiovascular disease; complement deposition; concentration response; controlled study; coronary artery; drug effect; genetic transfection; human; human cell; immunoregulation; nonhuman; protein expression; protein protein interaction; rat; red wine; upregulation; vascular endothelial cell
DOI:
10.1016/j.bbrep.2019.100652
