Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2373-2378
© 2000 American Heart Association, Inc.
Vascular Biology |
Phosphatidylinositol 3-Kinase Signaling Is Important for Smooth Muscle Cell Replication After Arterial Injury
From the Department of Pathology, University of Washington, Seattle.
Correspondence to Michael A. Reidy, PhD, Department of Pathology, University of Washington, Box 357335, Seattle WA 98195. E-mail mar1{at}u.washington.edu
Abstract—The phosphoinositide 3-kinase [PI(3)K] pathway is a key signaling pathway important for replication of mammalian cells. In this study, we examined the role of PI(3)K in smooth muscle cell (SMC) replication after balloon catheter injury of rat carotid arteries. Protein kinase B (PKB), a downstream target of PI(3)K, was phosphorylated at 30 and 60 minutes after injury and to a lesser degree after 6 hours and 1 and 2 days but not after 7 days. Wortmannin (10 µg per rat), a PI(3)K inhibitor, given to rats 60 and 5 minutes before and 11 hours after balloon injury, reduced the levels of phosphorylated PKB. SMC replication quantified between 24 to 48 hours was significantly reduced compared with control replication, as were the levels of cyclin D1. Wortmannin was also administered to rats between days 7 and 8 and between days 7 and 9 after balloon catheter injury. A reduction in levels of phosphorylated PKB was detected, but no decrease in the replication of intimal SMCs was observed in either experiment. These data demonstrate that the PI(3)K signal transduction pathway plays an important role in medial but not intimal SMC replication.
Key Words: balloon injury • smooth muscle cell replication • protein kinase B • wortmannin
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