Background: Heart failure is a clinical syndrome caused by underlying cardiac structural functional impairment, leading to insufficient cardiac output and abnormally elevated intracardiac pressures in both resting and stress conditions. The stimulator of interferon genes (STING), a transmembrane protein in the endoplasmic reticulum, plays a pivotal role in initiating and sustaining chronic inflammatory responses. Aim: We investigated whether macrophage-derived STING contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Methods and Results: Activated STING was detected in heart tissues of HFpEF mice. To study macrophage-cardiomyocyte interactions, we constructed a co-culture system bone marrow-derived macrophages (BMDMs) and HL-1 cardiomyocytes. STING activation in BMDMs, either via a gain-of-function mutation or an agonist, promoted hypertrophy co-cultured HL-1 cells. Mechanistically, macrophage STING activation increased Z-DNA binding protein 1 (ZBP1) expression in HL-1 cells and facilitated ZBP1-mediated inflammasome assembly. Conclusion: These findings provide novel insight into HFpEF pathogenesis and suggest that macrophage STING may serve as a potential therapeutic target.
[1]Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Pharm,Med Sch, Nanjing 210008, Jiangsu, Peoples R China.
[2]China Pharmaceut Univ, Sch Pharm, Dept Pharmacol, Nanjing 211198, Jiangsu, Peoples R China.
[3]Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Cardiol,Med Sch, Nanjing 210008, Jiangsu, Peoples R China.
[4]Nanjing Univ Chinese Med, Nanjing Drum Tower Hosp, Dept Cardiol, Nanjing 210023, Jiangsu, Peoples R China.
[5]Wenzhou Cent Hosp, Dept Emergency Med, Wenzhou 325000, Zhejiang, Peoples R China.
[6]Chinese Acad Sci, Univ Chinese Acad Sci, Inst Canc & Basic Med, Dept Pharm,Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China.
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