Abstract |
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-1alpha. In an in vitro flow chamber system, t-RESV (1-10 microM) 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-kappaB. 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.
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Authors | Cristina Rius, May Abu-Taha, Carlos Hermenegildo, Laura Piqueras, Jose-Miguel Cerda-Nicolas, Andrew C Issekutz, Luís Estañ, Julio Cortijo, Esteban J Morcillo, Francisco Orallo, Maria-Jesus Sanz |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 185
Issue 6
Pg. 3718-27
(Sep 15 2010)
ISSN: 1550-6606 [Electronic] United States |
PMID | 20709957
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Inflammation Mediators
- NF-kappa B
- PPAR gamma
- Stilbenes
- Angiotensin II
- Resveratrol
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Topics |
- Angiogenesis Inhibitors
(administration & dosage, chemistry, pharmacology)
- Angiotensin II
(antagonists & inhibitors, physiology)
- Animals
- Cardiovascular Diseases
(immunology, metabolism, pathology)
- Cell Communication
(drug effects, immunology)
- Cells, Cultured
- Disease Models, Animal
- Endothelium, Vascular
(drug effects, immunology, pathology)
- Female
- Humans
- Inflammation Mediators
(administration & dosage, chemistry, pharmacology)
- Male
- NF-kappa B
(antagonists & inhibitors, metabolism)
- Ovariectomy
- PPAR gamma
(biosynthesis)
- Rats
- Rats, Sprague-Dawley
- Resveratrol
- Stereoisomerism
- Stilbenes
(administration & dosage, chemistry, pharmacology)
- Up-Regulation
(drug effects, immunology)
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