Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells

Abstract

Endothelial cell (EC) injury and the response of EC and smooth muscle cells (SMCs) to injury contribute to the pathophysiology in patients with vascular disease and atherosclerosis. Since platelets have been suggested to play an important role in modulating vascular injury, the present study was undertaken to examine the influence and mechanism of action of individual platelet factors on bovine aortic EC and SMC migration using an in vitro wound assay system. Serotonin decreased EC proliferation and reduced EC migration 21 ± 1% (p < 0.005), which was attenuated by imipramine. Transforming growth factor-β reduced EC proliferation and decreased EC migration 52 ± 3% (p < 0.005). Norepinephrine increased EC proliferation but decreased EC migration 26 ± 2% (p < 0.005), which was abolished by phenoxybenzamine. Histamine increased EC proliferation but reduced EC migration 29 ± 2% (p < 0.005), which was attenuated by diphenhydramine. Platelet-derived growth factor decreased EC proliferation and decreased EC migration 40 ± 2% (p < 0.005). In contrast, serotonin increased SMC proliferation and increased SMC migration 31 ± 2% (p < 0.005), which was abolished by ketanserin. Transforming growth factor-β increased SMC migration 35 ± 5% (p < 0.005). Norepinephrine increased SMC proliferation and increased SMC migration 43 ± 4% (p < 0.005), which was abolished by propranolol. Histamine increased SMC proliferation and increased SMC migration 38 ± 3% (p < 0.005), which was abolished by cimetidine. Platelet-derived growth factor increased SMC proliferation and increased SMC migration 40 ± 3% (p < 0.005). Changes in migration were unaffected by growth-arresting treatment. Hence, these individual platelet factors inhibit EC migration and augment SMC migration via specific receptors and independent of proliferation changes. These results suggest mechanisms in which platelet factors may contribute to blood vessel injury in vivo.