Basic fibroblast growth factor reverses atherosclerotic impairment of human coronary angiogenesis-like responses in vitro.
The influence of atherosclerosis on vascular growth in humans was evaluated in an in vitro model of angiogenesis. Coronary artery intima-media explants from patients (n = 10) with coronary artery disease (CAD) (in all cases Stary type V lesions) and patients without CAD (n = 10) were cultured in a collagen matrix containing serum-free medium. Endothelial cell growth from explants was organized as capillary-like microtubes (CLM); the sum of their lengths was morphometrically quantitated as an index of angiogenesis. CLM growth was suppressed in CAD explants (n = 120), the index values at two weeks averaging only 20% +/- 3% of non-CAD explants (n = 120, P < 0.001). Addition of exogenous basic fibroblast growth factor (bFGF) (10 ng/ml) stimulated CLM growth substantially more in the CAD than in the non-CAD group, whereas bFGF-neutralizing antibodies nearly abolished growth in both. Endothelial cells isolated from non-CAD coronary arteries exhibited in culture typical endothelial characteristics, including cobblestone appearance, staining for von Willebrand factor, CLM formation on Matrigel substrate, and sensitivity to bFGF and to bFGF-neutralizing antibody. Inhibition of cell replication by oxidized low-density lipoprotein (OxLDL) was reversed by bFGF. We conclude that human atherosclerosis is associated with impairment of angiogenesis-like endothelial growth and that decreased bFGF availability contributes to the impairment.
Chen
C H
CH
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Nguyen
H H
HH
Weilbaecher
D
D
Luo
S
S
Gotto
A M
AM
Henry
P D
PD
D002452:Cell Count; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D005346:Fibroblast Growth Factors