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

• Main Authors: Chao-Feng Lin, Chih-Jou Su, Jia-Hong Liu, Shui-Tien Chen, Han-Li Huang, Shiow-Lin Pan
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Journal of Clinical Medicine
• Subjects: myocardial infarction; cardiac fibrosis; CXCL9; CCL20; isoproterenol
• Online Access: https://www.mdpi.com/2077-0383/8/5/659

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.