ANP and BNP but not VEGF are regionally overexpressed in ischemic human myocardium.
Angiogenic gene therapy in angina pectoris has been disappointing so far. Reasons might be that the administered genes already are overexpressed in ischemic myocardium, or that atrial and brain natriuretic peptides (ANP and BNP) are overexpressed, as they have anti-angiogenic effects. Five stable angina pectoris patients without heart failure were studied. Left ventricular biopsies were taken during coronary by-pass surgery from a region with stress-inducible ischemia and from a normal region. Both ANP and BNP but not vascular endothelial growth factor (VEGF) and VEGF-receptor 1 and 2 were overexpressed in ischemic regions compared to non-ischemic regions as measured by real-time PCR. The expression of 15 other angiogenic genes measured by oligonucleotide arrays was not consistently increased in ischemic regions. The overexpression of ANP and BNP suggests an anti-angiogenic effect in ischemic heart disease. The lack of overexpression of angiogenic genes supports the concept of therapeutic overexpression of these genes.
Rück
Andreas
A
Department of Medicine, Section of Cardiology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. andreas.ruck@medhs.ki.se
Gustafsson
Thomas
T
Norrbom
Jessica
J
Nowak
Jacek
J
Källner
Göran
G
Söderberg
Magnus
M
Sylvén
Christer
C
Drvota
Viktor
V
D000368:Aged; D000787:Angina Pectoris / Q000150:complications / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor