Myocardial gene expression of angiogenic factors in human chronic ischemic myocardium: influence of acute ischemia/cardioplegia and reperfusion.
OBJECTIVE
Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression.


METHODS
Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors.


RESULTS
There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium.


CONCLUSIONS
These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium.
Wang
Yongzhong
Y
Medical Department B, Cardiac Catheterization Laboratory, the Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark.
Gabrielsen
Anders
A
Lawler
Patrick R
PR
Paulsson-Berne
Gabrielle
G
Steinbrüchel
Daniel A
DA
Hansson
Goran K
GK
Kastrup
Jens
J
D000368:Aged; D000787:Angina Pectoris / Q000473:pathology; D042501:Angiogenic Proteins / Q000235:genetics*; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D006324:Heart Arrest, Induced; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015424:Reperfusion; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics
D042501:Angiogenic Proteins; D012333:RNA, Messenger; C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C