Circulating mitochondria promoted endothelial cGAS-derived neuroinflammation in subfornical organ to aggravate sympathetic overdrive in heart failure mice.

ABSTRACT:

Background

Sympathoexcitation contributes to myocardial remodeling in heart failure (HF). Increased circulating pro-inflammatory mediators directly act on the Subfornical organ (SFO), the cardiovascular autonomic center, to increase sympathetic outflow. Circulating mitochondria (C-Mito) are the novel discovered mediators for inter-organ communication. Cyclic GMP-AMP synthase (cGAS) is the pro-inflammatory sensor of damaged mitochondria.

Objectives

This study aimed to assess the sympathoexcitation effect of C-Mito in HF mice via promoting endothelial cGAS-derived neuroinflammation in the SFO.

Methods

C-Mito were isolated from HF mice established by isoprenaline (0.0125 mg/kg) infusion via osmotic mini-pumps for 2 weeks. Structural and functional analyses of C-Mito were

SUBMITTER: Zhang S 

PROVIDER: S-EPMC10799549 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature