Phosphatidylinositol 3-Kinase Signaling Is Important for Smooth Muscle Cell Replication After Arterial Injury

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 20; no. 11; pp. 2373 - 2378
• Main Authors: Shigematsu, Kunihiro, Koyama, Hiroyuki, Olson, N Eric, Cho, Aesim, Reidy, Michael A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.11.2000; Hagerstown, MD Lippincott
• Subjects: Androstadienes - pharmacology; Animals; Biological and medical sciences; Carotid Arteries - enzymology; Carotid Arteries - metabolism; Carotid Arteries - pathology; Catheterization - adverse effects; Cell Division - drug effects; Cyclin D1 - antagonists & inhibitors; Cyclin D1 - biosynthesis; Diseases of the cardiovascular system; Enzyme Inhibitors - pharmacology; Male; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - physiology; Phosphorylation - drug effects; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Tunica Intima - enzymology; Tunica Intima - pathology; Wortmannin; Cell proliferation; Rat; Enzyme; Pathogenesis; Transferases; Rodentia; Instrumentation therapy; Smooth muscle; Instrumental dilatation; Artery; Restenosis; Phosphatidylinositol; Vertebrata; Mammalia; Treatment; Kinase; Animal; Complication
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.atv.20.11.2373

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.