1. Academic Validation
  2. Potential Effects of CXCL9 and CCL20 on Cardiac Fibrosis in Patients with Myocardial Infarction and Isoproterenol-Treated Rats

Potential Effects of CXCL9 and CCL20 on Cardiac Fibrosis in Patients with Myocardial Infarction and Isoproterenol-Treated Rats

  • J Clin Med. 2019 May 11;8(5):659. doi: 10.3390/jcm8050659.
Chao-Feng Lin 1 2 3 Chih-Jou Su 4 Jia-Hong Liu 5 Shui-Tien Chen 6 Han-Li Huang 7 Shiow-Lin Pan 8 9 10
Affiliations

Affiliations

  • 1 Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110, Taiwan. thcpci@gmail.com.
  • 2 Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan. thcpci@gmail.com.
  • 3 Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, Taiwan. thcpci@gmail.com.
  • 4 Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110, Taiwan. jojocat127@gmail.com.
  • 5 Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. horng428@gmail.com.
  • 6 Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan. bcchen@gate.sinica.edu.tw.
  • 7 TMU Biomedical Commercialization Center, Taipei Medical University, Taipei 110, Taiwan. hlhuang@tmu.edu.tw.
  • 8 Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. slpan@tmu.edu.tw.
  • 9 TMU Biomedical Commercialization Center, Taipei Medical University, Taipei 110, Taiwan. slpan@tmu.edu.tw.
  • 10 Ph.D. Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. slpan@tmu.edu.tw.
Abstract

The chemokines CXCL9 and CCL20 have been reported to be associated with ventricular dysfunction. This study was aimed to investigate the effects of CXCL9/CCL20 on cardiac fibrosis following myocardial infarction (MI). Blood samples of patients with MI were obtained to determine the serum CXCL9, CCL20, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). The expression of CXCL9 and CCL20 in hypoxia-incubated H9c2 cells and TNF-α/TGF-β-activated peripheral blood mononuclear cells (PBMCs) were examined. The experimental MI of rats was produced by the intraperitoneal injection of isoproterenol (ISO) (85 mg/kg/day) for two consecutive days. The growth and migration of CXCL9/CCL20-incubated cardiac fibroblasts in vitro were evaluated. TNF-α/TGF-β-activated PBMCs showed an enhanced expression of CXCL9 and CCL20, while hypoxic H9c2 cells did not. Patients with MI had significantly enhanced levels of serum TGF-β and CXCL9 compared to healthy subjects. ISO-treated rats had increased serum CXCL9 levels and marked cardiac fibrosis compared to control rats. The trend of increased serum CCL20 in patients with MI and ISO-treated rats was not significant. CXCL9-incubated cardiac fibroblasts showed enhanced proliferation and migration. The findings of this study suggest that an enhanced expression of CXCL9 following MI might play a role in post-MI cardiac fibrosis by activating cardiac fibroblasts.

Keywords

CCL20; CXCL9; cardiac fibrosis; isoproterenol; myocardial infarction.

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