Resveratrol Calms Aging Blood Vessel Inflammation by Targeting the miR-217/SIRT1 Pathway in Mice and Cells

Vascular aging is a major contributor to cardiovascular disease, and chronic low-grade inflammation in the endothelium, the cell layer lining blood vessels, is increasingly seen as a driver. The NLRP3 inflammasome, an immune signaling complex, is one suspected culprit. Resveratrol has long been studied as an anti-aging compound, but how it might restrain this inflammation in aging vessels is not well mapped.

Researchers fed male C57BL/6 mice a regular diet supplemented with 0.04% resveratrol for 64 consecutive weeks and examined the naturally aged thoracic aorta. They then used human umbilical vein endothelial cells (HUVECs) made senescent with hydrogen peroxide, applying SIRT1 knockdown, resveratrol pretreatment, and miR-217 mimics or inhibitors to dissect the pathway.

In mice, resveratrol lowered body weight, improved endothelial function, increased SIRT1, and decreased miR-217, NOX4, and NLRP3 in the aorta. In cells, it dose-dependently reduced NOX4, spliced XBP1 (XBP1s), and reactive oxygen species. Silencing SIRT1 activated NLRP3 by upregulating NOX4 and XBP1s, an effect partially blunted by resveratrol. Resveratrol also suppressed the miR-217 rise caused by hydrogen peroxide. The miR-217 mimic promoted senescence, resveratrol mitigated this, and the miR-217 inhibitor further amplified the protective effect.

Taken together, the data support a model in which resveratrol lowers miR-217, restores SIRT1, reduces oxidative and ER-stress signaling, and thereby limits NLRP3 inflammasome activation in senescent endothelium. This suggests miR-217 and SIRT1 as potential therapeutic targets for vascular aging.

Caveats are important: this is preclinical work in male mice and an artificial oxidative-stress cell model, based only on the abstract. Resveratrol effects were only partial in places, the dose is not directly translatable to humans, and clinical benefit has not been shown.