STING Facilitates Vascular Calcification via p‐STAT1/NLRP3 Signal

• DOI: 10.1096/fj.202403334r
• Publication Date: 2025-04-07T20:26:00Z
• Authors: Lihe Lu; Xiaoyu Liu; Yuan Gong; Xingchen Zhou; An Chen; Mingxi Li; Liyun Feng; Zirong Lan; Yuanzhi Ye; Qingchun Liang; Jianyun Yan
• Keywords: Sting

ABSTRACT Vascular calcification is an independent predictor of cardiovascular mortality in patients with chronic kidney disease (CKD), yet no approved treatment exists. The cGAS‐STING signaling participates various diseases. Notably, DNA damage, important regulator vascular calcification, activates the signaling. However, it remains poorly understood whether STING regulates under CKD conditions. In current study, we showed that expression was elevated during calcification. knockdown or pharmacological inhibition decreased calcium deposits smooth muscle cells and human arterial rings, while its activation exacerbated Furthermore, knockout mice exhibited reduced aortic RNA sequencing analysis suggested STAT1 pathway may mediate STING‐induced phosphorylated (p‐STAT1) levels, p‐STAT1 mitigated VSMCs tissues. Additionally, downregulated NLRP3 expression, inhibiting further attenuated VSMC indicating accelerates via activation. Altogether, our study highlights STING/p‐STAT1/NLRP3 axis as a key mediator suggesting targeting represent promising therapeutic approach for patients.