Title: The effect of protein kinase C and its alpha subtype on human vascular smooth muscle cell proliferation, migration and fibronectin production
Abstract: Background: Vascular smooth muscle cell (SMC) migration, proliferation and extracellular matrix protein production are key steps in the formation of intimal hyperplasia, a process that leads to failure of vascular reconstructions. Protein kinase C (PKC) may be involved in all 3 cellular events. PKC consists of a family of 11 isotypes, 8 of which we have identified in human vascular SMCs. In this study we evaluate the role of PKCα as a second messenger for proliferation, migration and fibronectin production induced by human saphenous vein SMCs. Methods: DNA synthesis was evaluated by using 3H-thymidine incorporation. Mitogen-activated protein kinase (MAP-K) activation was quantified by Western blotting with an antibody to its phosphorylated substrate, Elk-1. Chemotaxis was evaluated by using a microchemotaxis chamber. SMC fibronectin was measured by Western blotting. For all experiments, PKCα was blocked with a selective inhibitor, Gö6976. Results: Gö6976, at concentrations that allow selective inhibition of PKCα, inhibited platelet-derived growth factor–stimulated SMC proliferation and MAP-K activation by 30% to 40% and 30% to 60%, respectively. SMC chemotaxis was stimulated approximately 2-fold by the PKCα inhibitor. Neither basal nor transforming growth factor–βI induced fibronectin production was affected by Gö6976. Conclusions: Our data suggest that PKCα is a positive mediator of SMC proliferation and MAP-K activity, a negative regulator of migration and has no effect on SMC fibronectin production. These data suggest that modulating activities of specific PKC isotypes might be useful in both the study and control of intimal hyperplasia. (Surgery 2000;128:192-7.)
Publication Year: 2000
Publication Date: 2000-08-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 27
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