2. Academic Validation
  3. PCSK9 regulates myofibroblast transformation through the JAK2/STAT3 pathway to regulate fibrosis after myocardial infarction

PCSK9 regulates myofibroblast transformation through the JAK2/STAT3 pathway to regulate fibrosis after myocardial infarction

  • Biochem Pharmacol. 2023 Dec 26:115996. doi: 10.1016/j.bcp.2023.115996.
Hailong Bao 1,  Xu Wang 2,  Haiyan Zhou 2,  Wei Zhou 2,  Fujun Liao 2,  Fang Wei 2,  Shiyu Yang 3,  Zhenhua Luo 4,  Wei Li 5
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China; Department of Cardiovascular Medicine, Gui Qian International General Hospital, Guiyang 550018, Guizhou, China.
  • 2 Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China; The Key Laboratory of Myocardial Remodeling Research, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China.
  • 3 Department of Cardiovascular Medicine, Gui Qian International General Hospital, Guiyang 550018, Guizhou, China.
  • 4 Department of Central Lab, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, China. Electronic address: 1106091568@qq.com.
  • 5 Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China; The Key Laboratory of Myocardial Remodeling Research, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China. Electronic address: liwei249188@sina.com.
PMID: 38154546 DOI: 10.1016/j.bcp.2023.115996
Abstract

Cardiac fibrosis is pivotal in the progression of numerous cardiovascular diseases. This phenomenon is hallmarked by an excessive deposition of ECM protein secreted by myofibroblasts, leading to increased myocardial stiffness. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine Protease that belongs to the proprotein-converting Enzyme family. It has emerged as a viable therapeutic target for reducing plasma low-density lipoprotein Cholesterol. However, the exact mechanism via which PCSK9 impacts cardiac fibrosis remains unclear. In the present research, an increase in circulating PCSK9 protein levels was observed in individuals with myocardial infarction and rat models of myocardial infarction. Moreover, the inhibition of circulating PCSK9 in rats was found to reduce post-infarction fibrosis. In vitro experiments further demonstrated that overexpression of PCSK9 or stimulation by extracellular PCSK9 recombinant protein enhanced the transformation of cardiac fibroblasts to myofibroblasts. This process also elevated collagen Ⅰ, and Ⅲ, as well as α-SMA protein levels. However, these effects were countered when co-incubated with the STAT3 Inhibitor S3I-201. This study suggests that PCSK9 may function as a novel regulator of myocardial fibrosis, primarily via the JAK2/STAT3 pathway.

Keywords

Cardiac fibrosis; Myocardial infarction; Myofibroblast transformation; Proprotein convertase subtilisin/kexin type 9.

Figures
Products
Inhibitors & Agonists
Other Products