STING Facilitates Vascular Calcification via p-STAT1/NLRP3 Signal

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Nephrology

Background:

• Vascular calcification is a major risk factor for cardiovascular mortality in chronic kidney disease (CKD) patients.
• The cGAS-STING pathway is implicated in cardiovascular diseases, and DNA damage activates it, but its role in CKD-related vascular calcification is unclear.

Purpose of the Study:

• To investigate the role of STING signaling in vascular calcification under CKD conditions.
• To explore the underlying molecular mechanisms, including the involvement of STAT1 and NLRP3.

Main Methods:

• Examined STING expression in vascular calcification models.
• Utilized STING knockdown, pharmacological inhibition, and knockout mice.
• Conducted RNA sequencing, Western blotting, and calcium deposition assays.
• Investigated the effects of p-STAT1 and NLRP3 inhibition.

Main Results:

• STING expression was elevated during vascular calcification.
• STING inhibition or knockdown reduced calcium deposits in cells and tissues, while activation worsened calcification.
• STING knockout mice showed decreased aortic calcification.
• The STING/p-STAT1/NLRP3 signaling axis was identified as a key mediator, with STING activating p-STAT1 and NLRP3.

Conclusions:

• STING plays a critical role in promoting vascular calcification in CKD.
• The STING/p-STAT1/NLRP3 signaling pathway is a significant mediator of this process.
• Targeting STING presents a potential therapeutic strategy for vascular calcification in CKD patients.