1. Academic Validation
  2. PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway

PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK/P53 signaling pathway

  • Cell Signal. 2023 Nov 14:110974. doi: 10.1016/j.cellsig.2023.110974.
Chanyuan Lv 1 Liuyi Zhou 2 Yongkang Meng 2 Haitao Yuan 3 Jing Geng 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; JiNan Key Laboratory of Cardiovascular Disease, Shandong 250021, China. Electronic address: 202135720@mail.sdu.edu.cn.
  • 2 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; JiNan Key Laboratory of Cardiovascular Disease, Shandong 250021, China.
  • 3 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; JiNan Key Laboratory of Cardiovascular Disease, Shandong 250021, China. Electronic address: yuanhaitao@sdfmu.edu.cn.
  • 4 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; JiNan Key Laboratory of Cardiovascular Disease, Shandong 250021, China. Electronic address: geng_jing@126.com.
Abstract

Background: Cardiac hypertrophy is studied in relation to energy metabolism, Autophagy, and Ferroptosis, which are associated with cardiovascular adverse events and chronic heart failure. Protein kinase D (PKD) has been shown to play a degenerative role in cardiac hypertrophy. However, the role of Ferroptosis in PKD-involved cardiac hypertrophy remains unclear.

Methods: A cardiac hypertrophy model was induced by a subcutaneous injection of angiotensin II (Ang II) for 4 weeks. Adeno-associated virus serotype 9 (AAV9)-PKD or AAV9-Negative control were injected through the caudal vein 2 weeks prior to the injection of Ang II. The degree of cardiac hypertrophy was assessed using echocardiography and by observing cardiomyocyte morphology. Levels of Ferroptosis and protein expression in the Jun N-terminal kinase (JNK)/P53 signaling pathway were measured both in vivo and in vitro.

Results: The results indicated that PKD knockdown reduces Ang II-induced cardiac hypertrophy, enhances cardiac function and inhibits Ferroptosis. The involvement of the JNK/P53 pathway in this process was further confirmed by in vivo and in vitro experiments.

Conclusion: In conclusion, our findings suggest that PKD knockdown mitigates Ang II-induced cardiac hypertrophy and Ferroptosis via the JNK/P53 signaling pathway.

Keywords

Cardiac hypertrophy; Ferroptosis; JNK/P53 signaling pathway; Protein kinase D.

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