From the First Department of Internal Medicine, Kobe University School of
Medicine, Kobe, Japan.
Correspondence to Seinosuke Kawashima, MD, First Department of Internal Medicine, Kobe University School of Medicine, 7–5-1, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
Abstract—The precise regulation of
cell growth in the vascular wall maintains vascular integrity, and its
disruption leads to cardiovascular disorders including
atherosclerosis and restenosis. Vascular
endothelial growth factor (VEGF) is a specific mitogen
for endothelial cells, and endothelin-1 (ET-1) is known
to stimulate the proliferation of smooth muscle cells. The aim of this
study was to explore a potential interaction between VEGF and ET-1 on
each expression in vascular cells. VEGF enhanced preproET-1 mRNA
expression and ET-1 secretion in bovine aortic
endothelial cells (BAECs). Similarly, in rat vascular
smooth muscle cells (VSMCs), ET-1 enhanced VEGF mRNA expression and
stimulated VEGF secretion. ET-1–induced VEGF mRNA expression was
abolished by a selective ETA receptor
antagonist, BQ-485, but not by an ETB-selective
blocker, BQ-788. It was also inhibited by pretreatment with actinomycin
D but not by pretreatment with cycloheximide. Furthermore, the
actinomycin D chase experiment revealed that ET-1 did not alter VEGF
mRNA stability. Coculture of BAECs and VSMCs enhanced both ET-1 and
VEGF gene expression in these cells, and the conditioned media from
BAECs and VSMCs reproduced the augmentation of each gene expression,
which was partially inhibited by BQ-485 or an antibody specific to
VEGF. Our results indicate that VEGF and ET-1 have stimulatory
interactions on each expression, which may play an important role in
concomitant proliferation of endothelial and smooth
muscle cells in the vascular wall.
© 1998 American Heart Association, Inc.
Scientific Contributions
Stimulatory Interaction Between Vascular Endothelial Growth Factor and Endothelin-1 on Each Gene Expression
Key Words: endothelial growth factors • endothelin-1 • gene expression • coculture • atherosclerosis
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