A novel small molecule compound VCP979 improves ventricular remodeling in murine models of myocardial ischemia/reperfusion injury

Jing Liu, Qingshu Meng, Xiaoting Liang, Rulin Zhuang, Dongsheng Yuan, Xinyu Ge, Hao Cao, Fang Lin, Xin Gong, Huimin Fan, Binghui Wang, Xiaohui Zhou, Zhongmin Liu

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Persistent ventricular remodeling following myocardial ischemia/reperfusion (MI/R) injury results in functional decompensation and eventual progression to heart failure. VCP979, a novel small-molecule compound developed in‑house, possesses anti‑inflammatory and anti‑fibrotic activities. In the present study, no significant pathological effect was observed following the administration of VCP979 on multiple organs in mice and no difference of aspartate transaminase/alanine aminotransferase/lactate dehydrogenase levels was found in murine serum. Treatment with VCP979 ameliorated cardiac dysfunction, pathological myocardial fibrosis and hypertrophy in murine MI/R injury models. The administration of VCP979 also inhibited the infiltration of inflammatory cells and the pro‑inflammatory cytokine expression in hearts post MI/R injury. Further results revealed that the addition of VCP979 prevented the primary neonatal cardiac fibroblasts (NCFs) from Angiotensin II (Ang II)‑induced collagen synthesis and neonatal cardiac myocytes (NCMs) hypertrophy. In addition, VCP979 attenuated the activation of p38‑mitogen‑activated protein kinase in both Ang II‑induced NCFs and hearts subjected to MI/R injury. These findings indicated that the novel small-molecule compound VCP979 can improve ventricular remodeling in murine hearts against MI/R injury, suggesting its potential therapeutic function in patients subjected to MI/R injury.

Original languageEnglish
Pages (from-to)353-364
Number of pages12
JournalInternational Journal of Molecular Medicine
Volume45
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Inflammation
  • MI/R injury
  • P38-MAPK
  • VCP979
  • Ventricular remodeling

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