Effect of basic fibroblast growth factor on the myocardial expression of hypoxia-inducible factor-1α and vascular endothelial growth factor following acute myocardial infarction

Heart Lung Circ. 2013 Nov;22(11):946-51. doi: 10.1016/j.hlc.2013.04.111. Epub 2013 May 18.

Abstract

Objective: To investigate the effect of basic fibroblast growth factor (bFGF) on myocardial expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) following acute myocardial infarction (AMI) in rats.

Methods: Eighty male Sprague-Dawley rats were divided into sham operation (n=20), AMI control (n=20), bFGF50 (intravenous bFGF 50 μg/kg/d, n=20) and bFGF200 (intravenous bFGF 200 μg/kg/d, n=20) groups. The left ventricular ejection fraction (LVEF) was measured by echocardiography. The expression of HIF-1α mRNA and VEGF mRNA in the ischaemic tissues was analysed by reverse transcription-polymerase chain reaction.

Results: The LVEF in the bFGF50 and bFGF200 group was higher than in the AMI control group (p<0.05) seven and 14 days after the treatment. There was no difference in HIF-1α mRNA expression between the bFGF50 and AMI control group (p>0.05). However, the HIF-1α mRNA expression in the bFGF200 group was higher than in the AMI control group seven days (1.13 ± 0.18 vs 0.90 ± 0.14, p<0.01) and 14 days (1.31 ± 0.18 vs 0.93 ± 0.09, p<0.01) after the treatment. The VEGF mRNA expression in the bFGF200 group was also higher than in the AMI control group seven days (1.10 ± 0.17 vs 0.86 ± 0.14, p<0.01) and 14 days after the AMI (1.28 ± 0.19 vs 0.89 ± 0.14, p<0.01).

Conclusions: bFGF therapy was associated with an improvement in left ventricular function and an increase in myocardial expression of HIF-1α mRNA and VEGF mRNA following AMI. bFGF may exert its cardioprotective effect through upregulating HIF-1α mRNA and VEGF mRNA in the ischaemic myocardium.

Keywords: Fibroblast growth factor; Hypoxia-inducible factor; Myocardial infarction; Rats; Vascular endothelial growth factor.

MeSH terms

  • Animals
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Male
  • Muscle Proteins / biosynthesis*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Muscle Proteins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Fibroblast Growth Factor 2