Circulation, Vol 88, 832-836, Copyright © 1993 by American Heart Association
Z Yang, G Noll and TF Luscher
BACKGROUND. Vascular smooth muscle cell proliferation is the key event of
coronary artery disease. Mechanical forces, in particular, pulsatile
stretch and platelet-derived growth factor, may play an important role.
METHODS AND RESULTS. Vascular smooth muscle cells were cultured from the
media of human left descending coronary arteries obtained from organ donors
using the explant method. To study effects of pulsatile stretch on vascular
smooth muscle cell proliferation, a computer- controlled in vitro pulsatile
stretch device was used. Cells were seeded onto Flex I culture plates with
deformable membranes and exposed to pulsatile stretch (60 cycles per
minute) and/or growth factors. Proliferation of smooth muscle cells was
determined by 3H-thymidine incorporation. Pulsatile stretch markedly
stimulated 3H-thymidine incorporation of coronary smooth muscle cells (180
+/- 15 to 432 +/- 27 cpm/10(5) cells; P < .05) after 24 hours and
increased cell number after 6 days (10.3 +/- 0.7 x 10(4)/mL; P < .05).
Platelet-derived growth factor-AB (0.01 to 10 ng/mL)
concentration-dependently stimulated 3H-thymidine incorporation in coronary
smooth muscle cells (EC50, 0.1 ng/mL) and had additive effects with
pulsatile stretch. The Ca2+ antagonist verapamil (10(-7) to 10(-5) M)
concentration- dependently inhibited proliferation stimulated by
platelet-derived growth factor back to control levels (P < .05 to .01)
but not that induced by pulsatile stretch. CONCLUSIONS. Pulsatile stretch
and platelet-derived growth factor are potent stimuli for proliferation of
coronary smooth muscle cells. The selective inhibitory effect of a Ca2+
antagonist on smooth muscle cell proliferation stimulated by platelet-
derived growth factor but not by pulsatile stretch may explain why the
drugs have only modest antiatherogenic effects in patients with coronary
artery disease.
ARTICLES
Calcium antagonists differently inhibit proliferation of human coronary smooth muscle cells in response to pulsatile stretch and platelet- derived growth factor
Department of Medicine, University Hospitals Basel, Switzerland.
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