Expression of cell cycle regulators during smooth muscle cell proliferation after balloon catheter injury of rat artery.
Intimal hyperplasia is defined as the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) with deposition of extracellular matrix. However, the cell cycle regulatory mechanisms of injury-induced VSMC proliferation are largely unknown. To examine the expression kinetics of cell cycle regulatory factors which is known to be worked positively or negatively, we used rat balloon injury model. Marked induction of proliferating cell nuclear antigen (PCNA), G1/S cyclin-dependent kinase (cdk2), and its regulatory subunit (cyclin E) occurred between 1 and 3 days after balloon arterial injury, and this was sustained for up to 7 days and then declined. However, the induction of the negative regulators, p21 and p27, occurred between 3 and 5 days of injury, peaked after 7 and 14 days and was then sustained. VSMC proliferation after balloon catheter injury of the rat iliac artery is associated with coordinated expression of positive (cdk2, cyclin E and PCNA) and negative (p21, p27) regulators. Cell cycle regulators such as cdk2, cyclin E, p21, p27 may be suitable targets for the control of intimal hyperplasia.
Chung
Jung Kee
JK
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Lee
Taeseung
T
Jung
In Mok
IM
Kim
Young Kyun
YK
Min
Seung Kee
SK
Suh
Jeong Wook
JW
Kim
Sang Joon
SJ
D000818:Animals; D001158:Arteries / Q000473:pathology*; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases / Q000096:biosynthesis; D002404:Catheterization / Q000009:adverse effects*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division; D019927:Cyclin E / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D006965:Hyperplasia / Q000473:pathology; D007083:Iliac Artery / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2