2. Academic Validation
  3. Prostaglandin I2 signaling prevents angiotensin II-induced atrial remodeling and vulnerability to atrial fibrillation in mice

Prostaglandin I2 signaling prevents angiotensin II-induced atrial remodeling and vulnerability to atrial fibrillation in mice

  • Cell Mol Life Sci. 2024 Jun 15;81(1):264. doi: 10.1007/s00018-024-05259-3.
Yue Zhang # 1,  Meng Yuan # 1,  Wenbin Cai 2,  Weiyan Sun 2,  Xuelian Shi 2,  Daiqi Liu 1,  Wenhua Song 1,  Yingqun Yan 3,  Tienan Chen 3,  Qiankun Bao 1,  Bangying Zhang 4,  Tong Liu 1,  Yi Zhu 5 6,  Xu Zhang 7 8,  Guangping Li 9 10
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Pingjiang Road 23rd, Tianjin, 300211, China.
  • 2 Tianjin Key Laboratory of Metabolic Diseases, Key Laboratory of Immune Microenvironment and Disease-Ministry of Education, Department of Physiology and Pathophysiology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Qixiang Tai Road 22nd, Tianjin, 300070, China.
  • 3 Department of Cardiac Surgery, The Second Hospital of Tianjin Medical University, Pingjiang Road 23rd, Tianjin, 300211, China.
  • 4 Department of Cardiology, First Affiliated Hospital of Kunming Medical University, Xichang Road 295th, Kunming, 650032, China.
  • 5 Tianjin Key Laboratory of Metabolic Diseases, Key Laboratory of Immune Microenvironment and Disease-Ministry of Education, Department of Physiology and Pathophysiology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Qixiang Tai Road 22nd, Tianjin, 300070, China. zhuyi@tmu.edu.cn.
  • 6 Department of Physiology and Pathophysiology, Tianjin Medical University, Qixiang Tai Road 22nd, Tianjin, 300070, China. zhuyi@tmu.edu.cn.
  • 7 Tianjin Key Laboratory of Metabolic Diseases, Key Laboratory of Immune Microenvironment and Disease-Ministry of Education, Department of Physiology and Pathophysiology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, Qixiang Tai Road 22nd, Tianjin, 300070, China. xuzhang@tmu.edu.cn.
  • 8 Department of Physiology and Pathophysiology, Tianjin Medical University, Qixiang Tai Road 22nd, Tianjin, 300070, China. xuzhang@tmu.edu.cn.
  • 9 Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Pingjiang Road 23rd, Tianjin, 300211, China. tjcardiol@126.com.
  • 10 Department of Cardiology, The Second Hospital of Tianjin Medical University, Pingjiang Road 23rd, Tianjin, 300211, China. tjcardiol@126.com.
  • # Contributed equally.
PMID: 38878214 DOI: 10.1007/s00018-024-05259-3
Abstract

Atrial fibrillation (AF) is the most common arrhythmia, and atrial fibrosis is a pathological hallmark of structural remodeling in AF. Prostaglandin I2 (PGI2) can prevent the process of fibrosis in various tissues via cell surface Prostaglandin I2 receptor (IP). However, the role of PGI2 in AF and atrial fibrosis remains unclear. The present study aimed to clarify the role of PGI2 in angiotensin II (Ang II)-induced AF and the underlying molecular mechanism. PGI2 content was decreased in both plasma and atrial tissue from patients with AF and mice treated with Ang II. Treatment with the PGI2 analog, iloprost, reduced Ang II-induced AF and atrial fibrosis. Iloprost prevented Ang II-induced atrial fibroblast collagen synthesis and differentiation. RNA-sequencing analysis revealed that iloprost significantly attenuated transcriptome changes in Ang II-treated atrial fibroblasts, especially mitogen-activated protein kinase (MAPK)-regulated genes. We demonstrated that iloprost elevated cAMP levels and then activated protein kinase A, resulting in a suppression of extracellular signal-regulated kinase1/2 and P38 activation, and ultimately inhibiting MAPK-dependent interleukin-6 transcription. In contrast, cardiac fibroblast-specific IP-knockdown mice had increased Ang II-induced AF inducibility and aggravated atrial fibrosis. Together, our study suggests that PGI2/IP system protects against atrial fibrosis and that PGI2 is a therapeutic target for treating AF.The prospectively registered trial was approved by the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2200056733. Data of registration was 2022/02/12.

Keywords

Atrial fibrillation; Atrial fibroblast; IL-6; IP receptor; Prostaglandin I2.

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