Inhibition of the
Proliferation of Smooth Muscle Cells From Human Coronary Bypass
Vessels by Vasonatrin Peptide
S. Y. LU1, M. Z. ZHU1, D. S. WANG2,
S. Y. CHEN3, W. D. ZHANG4, H. DONG3,
J. YU1, H. T. GUO1
1Department of Physiology, 2Department of
Anatomy, 3Department of Anesthesiology and 4Department
of Cardiovascular Surgery, Xi’jing Hospital, Fourth Military
Medical University, Xi’an, China
Received May 5, 2003
Accepted August 7, 2003
Summary
Abnormal proliferation of vascular smooth muscle cells (VSMCs)
is known to be a key event in the development of atherosclerosis
and restenosis. The present study examined the effect of a novel
synthetic natriuretic peptide, vasonatrin peptide (VNP), on
norepinephrine (NE)-induced proliferation of VSMCs from coronary
bypass vessels. Human VSMCs were isolated from an internal
mammary artery (IMA) and saphenous vein (SV) by explant culture
and stimulated with NE. MTT assay and [3H]
thymidine-incorporation were undertaken to analyze cell
proliferation and radioimmunoassay was used to determine the
level of intracellular cyclic 3’,5’-guanosine monophosphate
(cyclic GMP). NE (10-8 - 10-7 mol/l) had a
mitogenic effect in human VSMCs from both SV and IMA. However,
NE-stimulated proliferation of VSMCs from SV was greater than
that from IMA. Furthermore, low concentration of NE (10-10
mol/l) promoted cell growth in SV-derived cells but not in
IMA-derived cells. VNP (10-8 - 10-6 mol/l) reduced NE-induced
cell proliferation and increased intracellular cyclic GMP, which
were abrogated by HS-142-1. In addition, the growth inhibition
of VNP was mimicked by 8-bromo-cGMP. These results indicate that
VNP has a significant inhibitory effect on NE-stimulated
proliferation of human VSMCs from both IMA and SV, which is
mediated by guanylate cyclase-linked receptors by increasing
cyclic GMP.
Key words
Vasonatrin peptide • Vascular smooth muscle cells •
Proliferation
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