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

Chronic kidney disease (CKD) is well recognized as a distinct contributor to cardiac hypertrophy, while the un-derlying mechanism remains incompletely understood. Here, the authors show that myocardial mitochondrial oxidative damage is early and prominent in CKD and distinctively stimulates the STING-NFKB pathway by releasing mitochondrial DNA to drive cardiac hypertrophy. Furthermore, the authors reveal that ornithine decarboxylase (ODC1)-putrescine metabolic flux is transactivated by NFKB and is required for the STING-NFKB pathway to drive cardiac hypertrophy. Finally, genetic or pharmacologic inhibition of the myocardial mitochondria-STING-NFKB-ODC1 axis significantly prevents CKD-associated cardiac hypertrophy. Therefore, targeting the myocardial mitochoandria-STING-NFKB-ODC1 axis is a promising therapeutic strategy for cardiac hypertrophy in patients with CKD. (J Am Coll Cardiol Basic Trans Science 2022;7:820-840) (c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).