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  3. sGC agonist BAY1021189 promotes thoracic aortic dissection formation by accelerating vascular smooth muscle cell phenotype switch

sGC agonist BAY1021189 promotes thoracic aortic dissection formation by accelerating vascular smooth muscle cell phenotype switch

  • Eur J Pharmacol. 2023 May 25;175789. doi: 10.1016/j.ejphar.2023.175789.
Hongcheng Jiang 1,  Yue Jiang 2,  Yunkun Qu 3,  Jiagao Lv 4,  Hesong Zeng 5
Affiliations

Affiliations

  • 1 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China; Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, 430030, Hubei, China.
  • 2 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
  • 3 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. Electronic address: lujiagao@tjh.tjmu.edu.cn.
  • 5 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China; Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan, 430030, Hubei, China. Electronic address: zenghs@tjh.tjmu.edu.cn.
PMID: 37244376 DOI: 10.1016/j.ejphar.2023.175789
Abstract

Thoracic aortic dissection (TAD) is common but lethal Cardiovascular Disease with high mortality. This study aimed to expound whether and how sGC-PRKG1 signaling pathway might promote the formation of TAD. Our work identified two modules with high relevance to TAD using WGCNA method. Combined with previous studies, we focused on the participation of endothelial NOS (eNOS) in the progression of TAD. Through immunohistochemistry, immunofluorescence and western blot we verified that eNOS expression was elevated in the tissues of patients and mice with aortic dissection, and the phosphorylation Ser1177 of eNOS was activated. In a BAPN-induced TAD mouse model, sGC-PRKG1 signaling pathway promotes TAD formation by inducing vascular smooth muscle cells (VSMCs) phenotype transition, which was demonstrated as a decrease in markers of the contractile phenotype of VSMCs such as αSMA, SM22α, and Calponin. These results were also verified by experiments in vitro. To explore the further mechanism, we conducted immunohistochemistry, western blot and quantitative RT-PCR (qPCR), the results of which indicated that sGC-PRKG1 signaling pathway was activated when TAD occurred. In conclusion, our current study revealed that sGC-PRKG1 signaling pathway could promote TAD formation by accelerating VSMCs phenotype switch.

Keywords

Phenotype switch; Protein kinase cGMP-dependent type 1; Soluble guanylate cyclase; Thoracic aortic dissection; Vascular smooth muscle cell.

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