2. Academic Validation
  3. Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R

Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R

  • Redox Biol. 2024 Jun:72:103154. doi: 10.1016/j.redox.2024.103154.
Xin Zhong 1,  Kangwei Wang 1,  Yonghua Wang 2,  Luya Wang 1,  Sudan Wang 3,  Weijian Huang 1,  Zhuyin Jia 4,  Shan-Shan Dai 5,  Zhouqing Huang 6
Affiliations

Affiliations

  • 1 Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, WenZhou, ZheJiang, China.
  • 2 Department of Physical Education, WenZhou Medical University, WenZhou, ZheJiang, China.
  • 3 Department of Respiratory, Wenzhou People's Hospital of Zhejiang Province, WenZhou, ZheJiang, China.
  • 4 Department of Cardiology, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Wenzhou, Zhejiang, China. Electronic address: jzydexd@126.com.
  • 5 Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, Zhejiang, China. Electronic address: shanshandai137@163.com.
  • 6 Department of Cardiology and the Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital of WenZhou Medical University, WenZhou, ZheJiang, China. Electronic address: susiehzq@126.com.
PMID: 38626575 DOI: 10.1016/j.redox.2024.103154
Abstract

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that Ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 Receptor (P2X7R) activation plays a crucial role in numerous aspects of Cardiovascular Disease. The aim of this study was to elucidate any potential interactions between P2X7R and Ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and Ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

Keywords

Angiotensin II; Cardiac remodeling; Ferroptosis in myocytes; Human antigen R; Mutagenesis; P2X7R.

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