Dynamic changes in the expression of growth factor receptors in the myocardium microvascular endothelium after murine myocardial infarction.
BACKGROUND
After myocardial infarction, specific growth factors promote cardiac angiogenisis, leading to a therapeutic effect. Although this effect is mediated by specific receptors in the endothelium of the cardiac microvasculature, few studies have investigated dynamic changes in their expression. We explored this phenomenon in a murine model.


METHODS
We observed the mRNA expression of receptors by specific angiogenesis gene microarray at day 3 and day 7 after infarction. The vascular endothelial growth factor (VEGF) receptor Flk-1 was observed at the protein level at day 3 and day 7 by immunohistochemistry. The dynamic expression of fibroblast growth factor receptor-1 (FGFR-1) mRNA in the border zone and the noninfarcted zone at day 3, day 7, day 14, and day 42 was investigated by real-time PCR. Statistical significance was analyzed with SPSS 10.0 software using one-way analysis of variance (ANOVA).


RESULTS
Three days after infarction, 9 receptors in the border zone and 7 receptors in the noninfarcted zone were down-regulated. Two receptors in the infarct edge and 5 receptors in the distant myocardium were up-regulated. However, at day 7, 11 receptors in the border zone were up-regulated, and only one was down-regulated. In the border zone, Flk-1 levels decreased at day 3 but increased significantly at day 7. Real-time PCR showed that FGFR-1 mRNA decreased markedly in the border zone at day 3 but increased afterward for at least 6 weeks. In the early stage (3 days) after infarction, the expression of receptors had decreased to some extent. However, at day 7, receptor expression was active and had moved from the distant noninfarcted zone to the border zone as a part of the acute repair process.


CONCLUSIONS
Selecting the proper growth factors to target receptors with protective activity, and determining appropriate therapeutic timing may be important to the success of therapeutic angiogenesis.
Wang
Xin-hong
XH
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Zhang
Guo-ping
GP
Jin
Hui-ming
HM
Chen
Si-feng
SF
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D008833:Microcirculation; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*
D012333:RNA, Messenger; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1; D040301:Vascular Endothelial Growth Factor Receptor-2