Basic fibroblast growth factor reverses atherosclerotic impairment of human coronary angiogenesis-like responses in vitro

Chu Huang Chen, Hai Hoang Nguyen, Don Weilbaecher, Sherry Luo, Antonio Gotto, Philip D. Henry

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalAtherosclerosis
Volume116
Issue number2
DOIs
StatePublished - Aug 1995

Keywords

  • Angiogenesis
  • bFGF
  • Human coronary atherosclerosis
  • OxLDL

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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