Abstract
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.
Highlights
Complement mediated inflammation has recently been gaining emphasis as an important contributor to various forms of cardiovascular disease including atherosclerosis, coronary heart disease and heart failure [1]
Resveratrol concentrations ranging from 0.001 to 0.1 μM were chosen for an initial dose response experiment in human coronary artery endothelial cells (HCAECs) based on resveratrol and piceid concentration measurements obtained by UPLC-MS/MS in wine samples tested (Table 2)
The role of complement activation in cardiovascular disease prediction, emergence and progression has been demonstrated by numerous studies rendering it an important pathogenetic factor in cardiovascular disease
Summary
Complement mediated inflammation has recently been gaining emphasis as an important contributor to various forms of cardiovascular disease including atherosclerosis, coronary heart disease and heart failure [1]. Complement activation is, under control by several proteins known as complement regulatory proteins. Moderate wine consumption is widely recognised as protective against cardiovascular disease and is mainly attributed to phenolic stilbenes, exemplified by trans-resveratrol [3,5,4′-trihydroxy-trans-stilbene,(E)-5-(4-hydroxystyryl)benzene-1,3-diol], a naturally occurring phytoalexin widely known as resveratrol. The demonstration of a reverse relationship between wine consumption and cardiovascular disease [4], known as the ‘French paradox’, was mainly attributed to the various phenolic compounds of the stilbene family contained in wine, especially red wine. In 1992 [5] resveratrol was identified as a key red wine bioactive polyphenol and, based on extensive research, was implicated in conferring the protective effect of red wine against cardiovascular disease. Other health promoting effects linked to resveratrol include increased longevity and attenuation of diet-induced metabolic syndrome and diabetes [6,7,8]
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