Icariin influences cardiac remodeling following myocardial infarction by regulating the CD147/MMP-9 pathway

J Int Med Res. 2018 Jun;46(6):2371-2385. doi: 10.1177/0300060518762060. Epub 2018 May 7.

Abstract

Objective We investigated the protective effect of icariin on myocardial infarction-induced cardiac remodeling. Methods A cardiac remodeling model was constructed by ligating rats' coronary artery. Different icariin and CD147 concentrations were administered in the model group, and echocardiography was used to detect systolic function, screening out ideal experimental concentrations. The ventricular systolic function, myocardial apoptosis rate, and expression of collagen type I (Col I), Col III, CD147, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by hematoxylin-eosin staining, TUNEL assay, and western blot. MMP-9 activity was evaluated by gelatin zymography. Results The expression of Col I, Col III, CD147, and MMP-9 was higher, the expression of TIMP-1 was lower, and the maximal rates of left ventricular pressure rise and fall (+dp/dtmax and -dp/dtmax, respectively) were lower in model than control rats. The expression of CD147, MMP-9, Col I, and Col III was lower, the expression of TIMP-1 was higher, and the +dp/dtmax and -dp/dtmax were higher in the icariin than model group. The apoptosis rate was lower in the icariin and icariin + CD147 groups than control group. Conclusion Icariin attenuated myocardial apoptosis following myocardial infarction by apoptosis rate reduction and CD147/MMP-9 pathway inhibition.

Keywords: CD147/MMP-9 pathway; Myocardial infarction; apoptosis; cardiac remodeling; collagen; icariin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Basigin / metabolism*
  • Cardiovascular Agents / pharmacology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Flavonoids / pharmacology*
  • Matrix Metalloproteinase 9 / metabolism*
  • Models, Cardiovascular
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology*
  • Protective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Ventricular Remodeling / drug effects*
  • Ventricular Remodeling / physiology

Substances

  • Cardiovascular Agents
  • Drugs, Chinese Herbal
  • Flavonoids
  • Protective Agents
  • Basigin
  • Matrix Metalloproteinase 9
  • icariin