STIM1 deletion in regulatory T cells restores redox balance and protects against hypertension-induced cardiovascular complications.

BACKGROUND

Regulatory T cells (Tregs) play a protective role in cardiovascular diseases, but the redox-regulated mechanisms governing their survival remain unclear. Stromal interaction molecule 1 (STIM1), a key calcium sensor, is implicated in oxidative stress and T cell apoptosis. This study investigates how Treg-specific deletion of STIM1 modulates redox signaling and mitigates renovascular hypertension and associated cardiovascular complications.

METHODS

STIM1 was selectively deleted in Tregs using a Cre-loxP approach. Mice were subjected to 2-kidney-1-clip (2K1C) surgery to induce renovascular hypertension. Endpoints included blood pressure, cardiac and pulmonary pathology, endothelial function, redox markers (ROS, SOD, BH4), nitric oxide bioavailability, and inflammatory cytokines.

RESULTS

STIM1 deletion in Tregs prevented in vitro angiotensin II-induced Treg cell death and protected against in vivo hypertension, cardiac hypertrophy, endothelial dysfunction, and fibrosis. Interestingly, STIM1-deficient Tregs preserved eNOS phosphorylation and nitrate levels, reduced ROS, and restored SOD and BH4 levels. Inflammatory cytokines and TGF-β1 were also significantly attenuated in knockout mice.

CONCLUSIONS

STIM1 in Tregs is a significant mechanism of immune survival and redox homeostasis in renovascular hypertension. Its deletion alleviates oxidative stress, vascular injury, and fibrosis, highlighting a promising immuno-redox target for cardiovascular disease intervention.