Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis

Abstract

Recent studies have shown that resveratrol (3,5,4¢-trihydroxystilbene), a polyphenolic compound found in grapes and red wine, has various beneficial effects on cardiovascular diseases and prolongs the life span of mice fed a high-fat diet. We hypothesized that resveratrol may attenuate vascular inflammatory response induced by angiotensin (Ang) II. We examined the effect of resveratrol on Ang II-induced interleukin (IL)-6 expression in vascular smooth muscle cells (VSMCs). Resveratrol significantly attenuated Ang II-induced IL-6 mRNA expression and IL-6 protein in the supernatant of VSMC in a dose-dependent manner. Resveratrol suppressed the IL-6 gene promoter activity. Resveratrol inhibited the Ang II-induced cAMP-response element-binding protein and nuclear factor-kappa B activity, which are critical for Ang II-induced IL-6 gene activation. An increase in the serum concentration of IL-6 induced by Ang II infusion was attenuated by an oral administration of resveratrol. Resveratrol also inhibited Ang II-induced hypertension and perivascular fibrosis of the heart. Although hydralazine reduced blood pressure level equal to resveratrol, it did not reduce the Ang II-induced IL-6 production and perivascular fibrosis. These data suggest that the inhibition of Ang II-induced vascular inflammation and high blood pressure by resveratrol may contribute, at least in part, to the anti-atherogenic effects of resveratrol.

Sirt1 activation protects the mouse renal medulla from oxidative injury

“…The present findings show a beneficial role for Sirt1 in protecting the kidney from fibrosis, which supports previous studies showing an antifibrotic effect of resveratrol (51)(52)(53). Although the detailed mechanisms of renal fibrosis after ureteral obstruction are still incompletely understood, fibrosis appears to be a maladaptive response to injury.…”

Resveratrol Inhibits Monocytic Cell Chemotaxis to MCP-1 and Prevents Spontaneous Endothelial Cell Migration Through Rho Kinase-Dependent Mechanism

“…With regard to endothelial function, the majority of the atheroprotective activity of resveratrol was thus far believed to originate from the inhibition of pro-inflammatory signaling via suppression of NF-B activity 7,21,22) . In accordance with this, we previously demonstrated that resveratrol significantly inhibited adhesion molecule induction and monocytic cell adhesion to TNF--stimulated endothelial cells under hemodynamic conditions corresponding to these in atherosclerosis-prone arterial bifurcations 10) .…”

A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon

“…According to our previous experience 12 , the viscosity of the preparation was based on the non-ionic contrast medium iomeprol (Iomerol ® , Bracco, Italy; kinematic viscosity at 37°C: 5.617±0.034 mm 2 •s -1 ). The final kinematic viscosity of the RSV-c was very close to that of the reference solution (6.097±0.0379 mm 2 s -1 ).…”

“…There are several pioneering reports on RSV, including studies on the inhibition of the arachidonate metabolism via interactions with the 5-lipoxygenase and cyclooxygenase pathways in leukocytes [6][7][8][9][10][11][12] . However, RSV attracted little interest until 1979, when the "French Paradox" 13 reported the positive benefit of an RSV-containing diet, in particular the moderate consumption of red wine, for coronary heart disease.…”