Macrophage STING activation induces cardiomyocyte hypertrophy

Abstract

Background: Heart failure is a clinical syndrome caused by underlying cardiac structural or 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 of 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 of 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.

Keywords

HFpEF / STING / cardiomyocyte hypertrophy / BMDMs / ZBP1

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