NATRIURETIC PEPTIDE FAMILY AS A NOVEL ANTIMIGRATION FACTOR OF VASCULAR SMOOTH-MUSCLE CELLS

Vascular smooth muscle cell (SMC) migration is proposed to be an impor tant process in the initiation and/or progression of atherosclerosis. The present study examined the effects of the natriuretic peptide fami ly (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 inhibi tory effect compared with other natriuretic peptides. When PDGF-BB-ind uced migration was separated into chemotactic and chemokinetic activit ies, the chemotactic component was strongly inhibited by these natriur etic peptides. Such inhibition by these natriuretic peptides was paral leled 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 inhi bited FCS- and PDGF-BB-stimulated migration in a concentration-depende nt manner. These results suggest that natriuretic peptides, especially CNP-22, inhibit FCS- or PDGF-BB-stimulated SMC migration at least in part through a cyclic GMP-dependent process. Thus, the natriuretic pep tide family may play a role as an antimigration factor of SMCs under c ertain circumstances.