Zhoufei, F.; Han, C.; Liu, R.; Yu, L.; Chen, C.; Chen, S.; Li, l.; Chen, Q.; Cai, H.; Su, J.; Peng, F.

This study investigated the role and mechanism of microRNA-128 (miR-128) in hypertensive vascular remodeling, focusing on peroxisome proliferator-activated receptor {gamma} (PPAR-{gamma}) and the Toll-like receptor 4/nuclear factor{kappa}-B (TLR4/NF-{kappa}B) pathway. Ten-week-old male spontaneously hypertensive rats (SHRs) were randomly divided into renal denervation (RDN), sacubitril/valsartan, and sham groups; age-matched Wistar-Kyoto rats served as normotensive controls. Eight weeks after intervention, mesenteric arteries were collected for histological, functional, and molecular analyses.Serum miR-128 levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by immunofluorescence, immunohistochemistry, and Western blotting. Compared with the sham group, SHRs showed elevated blood pressure, severe vascular remodeling, and impaired vasodilation, accompanied by downregulated miR-128 and activated TLR4/NF-{kappa}B signaling (all p < 0.0001). RDN markedly restored miR-128 expression, suppressed the TLR4/NF-{kappa}B pathway and pro-inflammatory cytokines (IL-1{beta}, IL-6, TNF-), and improved vasodilatory function (all p < 0.0001). Mechanistically, miR-128 negatively regulated the TLR4/NF-B pathway by upregulating PPAR-{gamma} (p < 0.05). In conclusion, RDN attenuates hypertension and vascular remodeling. miR-128 alleviates vascular inflammation and remodeling via the PPAR-{gamma}/TLR4/NF-{kappa}B axis, representing a promising therapeutic target for hypertension.