期刊
JOURNAL OF IMMUNOLOGY
卷 185, 期 6, 页码 3718-3727出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001043
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资金
- Comision Interministerial de Ciencia y Tecnologia [SAF2008-03477, SAF2008-03113, SAF200908913]
- Spanish Ministry of Science and Innovation
- Carlos III Health Institute, Spanish Ministry of Health [FIS06/0589, PI081875, REDHERACLESRD06/0009/0005, RIER RD08/0075/0016]
- European Regional Development Fund
- Generalitat Valenciana [PROMETEO/2008/045, GVACOMP2010-129]
- Spanish Ministry of Foreign Affairs
Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II-induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i. v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1 alpha. In an in vitro flow chamber system, t-RESV (1-10 mu M) undermined the adhesion of human leukocytes under physiological flow to Ang-II-activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-kappa B. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-gamma in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-gamma also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease. The Journal of Immunology, 2010, 185: 3718-3727.
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