The REDD1-NF-κB-miRNAs-eNOS/SIRT1 axis mediates obesity-induced endothelial cell senescence and hypertension - PubMed
5 hours ago
- #endothelial senescence
- #obesity
- #hypertension
- The study identifies the REDD1-NF-κB-miRNAs-eNOS/SIRT1 axis as a key mediator in obesity-induced endothelial cell (EC) senescence and hypertension.
- Metabolic stress upregulates REDD1, which promotes EC senescence and hypertension via NF-κB-dependent induction of miR-155-5p and miR-214-3p, suppressing eNOS and SIRT1.
- In obese male mice, increased REDD1 and miR-214-3p levels correlate with decreased eNOS and SIRT1, leading to EC senescence, renal dysfunction, and hypertension.
- The phenotype is mitigated in mice lacking REDD1, EC-specific REDD1, or miR-214-3p, and in mice expressing a REDD1 mutant (KK219/220AA) that cannot activate atypical NF-κB.
- The findings suggest the REDD1-NF-κB-miRNAs-eNOS/SIRT1 axis as a promising therapeutic target for obesity-related vascular dysfunction.