NITRIC-OXIDE MEDIATES CYTOTOXICITY AND BASIC FIBROBLAST GROWTH-FACTORRELEASE IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS - A POSSIBLE MECHANISM OF NEOVASCULARIZATION IN ATHEROSCLEROTIC PLAQUES
K. Fukuo et al., NITRIC-OXIDE MEDIATES CYTOTOXICITY AND BASIC FIBROBLAST GROWTH-FACTORRELEASE IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS - A POSSIBLE MECHANISM OF NEOVASCULARIZATION IN ATHEROSCLEROTIC PLAQUES, The Journal of clinical investigation, 95(2), 1995, pp. 669-676
To define the pathophysiological role of nitric oxide (NO) released fr
om vascular smooth muscle cells (VSMC), we examined whether NO release
d from VSMC induces cytotoxicity in VSMC themselves and adjacent endot
helial cells (EC) using a coculture system. Prolonged incubation with
interleukin-1 (IL-1) induced large amounts of NO release and cytotoxic
ity in VSMC. N-G-Monomethyl-L-arginine, an inhibitor of NO synthesis,
inhibited both NO release and cytotoxicity induced by IL-1. In contras
t, DNA synthesis in cocultured EC was not inhibited but rather stimula
ted by prolonged incubation with IL-1 or sodium nitroprusside (SNP), a
NO donor. However, IL-1 and SNP did not stimulate but inhibited DNA s
ynthesis in EC alone. On the other hand, conditioned medium from VSMC
incubated for a long period with IL-1 or SNP stimulated DNA synthesis
in EC alone. Furthermore, the concentration of basic fibroblast growth
factor in the conditioned medium was increased and correlated with th
e degree of cytotoxicity in VSMC. These results indicate that NO relea
sed from VSMC induces VSMC death, which results in release of basic fi
broblast growth factor, which then stimulates adjacent EC proliferatio
n. Thus, NO released from VSMC may participate in the mechanism of neo
vascularization in atherosclerotic plaques.