Targeting Myocardial Mitochondria-STING-Polyamine Axis Prevents Cardiac Hypertrophy in Chronic Kidney Disease

Overview

Journal JACC Basic Transl Sci

Date 2022 Sep 5

PMID 36061341

Authors

Wenhao Han

Changhong Du

Yingguo Zhu

Li Ran

Yue Wang

Jiachuan Xiong

Yiding Wu

Qigang Lan

Yaqin Wang

Liting Wang

Junping Wang

Ke Yang

Jinghong Zhao

Affiliations

Soon will be listed here.

Abstract

Chronic kidney disease (CKD) is well recognized as a distinct contributor to cardiac hypertrophy, while the underlying mechanism remains incompletely understood. Here, the authors show that myocardial mitochondrial oxidative damage is early and prominent in CKD and distinctively stimulates the STING-NFκB pathway by releasing mitochondrial DNA to drive cardiac hypertrophy. Furthermore, the authors reveal that ornithine decarboxylase (ODC1)-putrescine metabolic flux is transactivated by NFκB and is required for the STING-NFκB pathway to drive cardiac hypertrophy. Finally, genetic or pharmacologic inhibition of the myocardial mitochondria-STING-NFκB-ODC1 axis significantly prevents CKD-associated cardiac hypertrophy. Therefore, targeting the myocardial mitochoandria-STING-NFκB-ODC1 axis is a promising therapeutic strategy for cardiac hypertrophy in patients with CKD.

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