Articles |
From the First Department of Internal Medicine (M.I., M.K., K. Yasunari, K. Yokokawa, T.H., J.Y.) and the First Department of Pathology (M.U.), Osaka City University Medical School, and the Second Department of Internal Medicine, School of Medicine, Chiba University (N.M.), Japan.
Correspondence to Masakazu Kohno, MD, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.
Abstract Vascular smooth muscle cell (SMC) migration is proposed to be an important process in the initiation and/or progression of atherosclerosis. The present study examined the effects of the natriuretic peptide family (atrial, brain, and C-type natriuretic peptides; ANP, BNP, and CNP) on the migration of cultured rat SMCs, using Boyden's chamber methods. Fetal calf serum (FCS) and platelet-derived growth factor (PDGF)-BB potently stimulated SMC migration. Rat ANP(1-28), rat BNP-45, and rat CNP-22 clearly inhibited SMC migration stimulated with FCS or PDGF-BB in a concentration-dependent manner. CNP-22 had the most potent inhibitory effect compared with other natriuretic peptides. When PDGF-BBinduced migration was separated into chemotactic and chemokinetic activities, the chemotactic component was strongly inhibited by these natriuretic peptides. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cyclic GMP. The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, and an activator of the cytosolic guanylate cyclase, sodium nitroprusside, significantly inhibited FCS- and PDGF-BBstimulated migration in a concentration-dependent manner. These results suggest that natriuretic peptides, especially CNP-22, inhibit FCS- or PDGF-BBstimulated SMC migration at least in part through a cyclic GMPdependent process. Thus, the natriuretic peptide family may play a role as an antimigration factor of SMCs under certain circumstances.
Key Words: natriuretic peptide, atrial, brain, and C-type migration smooth muscle cells
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