| Autor: |
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 |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
JACC. Basic to translational science. 7(8) |
| ISSN: |
2452-302X |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
