title: Cyclin-dependent kinase inhibitor, p21Waf1, regulates vascular smooth muscle cell hypertrophy.
abstract: In the process of vascular diseases, smooth muscle cells (SMC) undergo not only hyperplasia but also hypertrophy, resulting in vascular remodeling. A cyclin-dependent kinase inhibitor (CDKI), p21Waf1, has been shown to play an important role in SMC hyperplasia. Here we investigated a potential role of p21Waf1 in SMC hypertrophy. An exposure of cultured rat SMC to serum drove the cell cycle progression with up-regulation of various cell cycle markers and increased activities of cyclin-dependent kinases, but did not cause SMC hypertrophy. In contrast, incubation of SMC for 48 h with angiotensin II (AII, 100 nmol/l) resulted in a significant increase in the cell size measured by flowcytometric forward-angle light scatter assay, in association with an increase in the ratio of [3H]leucine/[3H]thymidine uptake, indicating SMC hypertrophy. At 48 h, p21Waf1 expression was up-regulated in SMC exposed to AII but not in those exposed to serum. These results suggest that p21Waf1 may be involved in hypertrophy. To further investigate this issue, two manipulations of the p21Waf1 gene were performed. Adenovirus-mediated over-expression of p21Waf1 not only reduced S-phasic cells but also caused hypertrophy, despite the exposure to serum. Antisense oligodeoxynucleotide for p21Waf1 inhibited the hypertrophy of SMC exposed to AII. Our data suggest that p21Waf1 may play a role in SMC hypertrophy as well.
authors.affiliation: Department of Internal Medicine III, Cardiovascular Research Institute, Kurume University, School of Medicine, Kurume, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Arima
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Minoru
authors.initials: M
authors.lastname: Morimatsu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001798:Blood Proteins / Q000494:pharmacology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005326:Fetal Proteins / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006965:Hyperplasia; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology*; D006984:Hypertrophy; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005326:Fetal Proteins; D025521:Tumor Suppressor Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D050760:Cyclin-Dependent Kinase Inhibitor p27