RESPONSE OF VASCULAR SMOOTH-MUSCLE CELLS TO THE NEUROPEPTIDE SECRETONEURIN - A FUNCTIONAL-ROLE FOR MIGRATION AND PROLIFERATION IN-VITRO

Mesenchymal cell migration and replication are central biologic events involved in atherosclerosis and lung and hepatic fibrosis. Tissue rep air and fibrosis are thought to be regulated by growth regulatory mole cules, comprising both stimulators and inhibitors of mesenchymal cell functions, including platelet-derived growth factor (PDGF), transformi ng growth factor-beta (TGF-beta), fibroblast growth factors, and sever al neuropeptides such as substance P. Secretoneurin (SN), a novel 33-a mino acid neuropeptide derived from secretogranin II (chromogranin C), is widely distributed in the central and peripheral nervous and neuro endocrine systems, including afferent C-fibers, and can be released in the periphery by capsaicin. Recently, we reported that SN triggers th e selective migration of human monocytes and fibroblasts in vitro, imp licating its involvement in inflammatory responses. We report herein t hat SN stimulates specific migration (maximal response at 10(-10) M) o f cultured arterial smooth muscle cells (SMCs), originating from rat t horacic aorta, and initiates DNA synthesis and SMC growth (BrdU incorp oration, MTT test) with a maximum at 10(-8) M SN to a similar extent a s observed by PDGF. Both functional activities of SN were inhibited by specific anti-SN immunoglobulins (dilution, 1:1000), and furthermore, a trypsinized SN peptide (10(-8) M) was unable to provoke biologic ef fects. Our studies suggest that SN functions as a regulatory peptide t o modulate SMC migration and proliferation, which in conjunction with other factors could serve to aggravate and accelerate the development of atherosclerotic or restenotic lesions at sites of vascular injury.