TY - JOUR
T1 - Inhibitory effects of hypercholesterolemia and Ox-LDL on angiogenesis- like endothelial growth in rabbit aortic explants
T2 - Essential role of basic fibroblast growth factor
AU - Chen, Chu Huang
AU - Cartwright, Joiner
AU - Li, Zheng
AU - Lou, Sherry
AU - Nguyen, Hai Hoang
AU - Gotto, Antonio
AU - Henry, Philip D.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - Hypercholesterolemic (HC) rabbits exhibit suppressed compensatory vascular growth after restriction of arterial supply. However, neovascularization is commonly found in atheromas containing inflammatory coils. We used an in vitro model to determine the effects of hypercholesterolemia on angiogenesis in the absence or presence of inflammatory cells. HC rabbit aortic explants (1 mm2) with or without (n=90 each) lesion-forming inflammatory cells were cultured in a collagen matrix with serum-free medium. Explant-derived endothelial cell growth was organized into capillary-like microtubes (CLM) that could be videomicroscopically quantified. CLM growth from lesion-free HC explants was significantly reduced to 13±4% of the value in explants (n=90) from normocholesterolemic (NC, n=15) rabbits (P<.001). In contrast, in lesion-containing HC explants, the matrix was invaded by foam cells, anti CLM growth was not inhibited. Immunoassayable basic fibroblast growth factor (bFGF, in pg/mL) in the culture medium was significantly lower in lesion-free HC (<5) than NC explants (11±2, P<.01) or HC explants with lesions (14±3). In addition, CLM growth was reduced in NC explants incubated with oxidized LDL (ox-LDL, 50- 100 μg/mL). Exogenous bFGF (10 ng/mL) reversed the inhibitory effects of hypercholesterolemia and ox-LDL, whereas bFGF-neutralizing antibody (10μg/mL) abolished CLM growth in all groups. In cultured rabbit aortic endothelial cells, ox-LDL reduced DNA synthesis, but this inhibition was reversed by bFGF. We conclude that hypercholesterolemia and ox-LDL inhibit angiogenesis-like endothelial growth because of a suppressed availability of endogenous bFGF. Retained responsiveness to exogenous bFGF suggests that inducing bFGF expression at targeted sites may improve collateral growth in hyperlipidemic arterial disease.
AB - Hypercholesterolemic (HC) rabbits exhibit suppressed compensatory vascular growth after restriction of arterial supply. However, neovascularization is commonly found in atheromas containing inflammatory coils. We used an in vitro model to determine the effects of hypercholesterolemia on angiogenesis in the absence or presence of inflammatory cells. HC rabbit aortic explants (1 mm2) with or without (n=90 each) lesion-forming inflammatory cells were cultured in a collagen matrix with serum-free medium. Explant-derived endothelial cell growth was organized into capillary-like microtubes (CLM) that could be videomicroscopically quantified. CLM growth from lesion-free HC explants was significantly reduced to 13±4% of the value in explants (n=90) from normocholesterolemic (NC, n=15) rabbits (P<.001). In contrast, in lesion-containing HC explants, the matrix was invaded by foam cells, anti CLM growth was not inhibited. Immunoassayable basic fibroblast growth factor (bFGF, in pg/mL) in the culture medium was significantly lower in lesion-free HC (<5) than NC explants (11±2, P<.01) or HC explants with lesions (14±3). In addition, CLM growth was reduced in NC explants incubated with oxidized LDL (ox-LDL, 50- 100 μg/mL). Exogenous bFGF (10 ng/mL) reversed the inhibitory effects of hypercholesterolemia and ox-LDL, whereas bFGF-neutralizing antibody (10μg/mL) abolished CLM growth in all groups. In cultured rabbit aortic endothelial cells, ox-LDL reduced DNA synthesis, but this inhibition was reversed by bFGF. We conclude that hypercholesterolemia and ox-LDL inhibit angiogenesis-like endothelial growth because of a suppressed availability of endogenous bFGF. Retained responsiveness to exogenous bFGF suggests that inducing bFGF expression at targeted sites may improve collateral growth in hyperlipidemic arterial disease.
KW - Angiogenesis
KW - Basic fibroblast growth factor
KW - Hypercholesterolemia
KW - Oxidized LDL
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U2 - 10.1161/01.ATV.17.7.1303
DO - 10.1161/01.ATV.17.7.1303
M3 - Article
C2 - 9261260
AN - SCOPUS:0030836338
SN - 1079-5642
VL - 17
SP - 1303
EP - 1312
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 7
ER -