[Regulation of cyclin-dependent kinase inhibitors by mitogen-activated protein kinase in angiotensin II-stimulated vascular smooth muscle cell hypertrophy].
OBJECTIVE
To investigate the role of mitogen-activated protein kinase (MAPK) in the regulation of cyclin-dependent kinase inhibitors (CDKI) in the process of vascular smooth muscle cell (VSMC) hypertrophy induced by angiotensin II stimulation.


METHODS
The medial layer of male SD rat aorta was isolated for VSMC culture. After cultured in serum-free medium to arrest the cell growth, VSMCs were stimulated with angiotensin II (1x10(-6) mol/L) or/and phorbol myristate acetate (PMA, 20 nmol/L), with the cells cultured in serum-free medium serving as control. MAPK activity of the cells was assayed 90 min after stimulation with immunoprecipitation test, and the expression levels of CDKI p27, p57 and p21 were determined by Western blotting 6 and 24 h after stimulation respectively.


RESULTS
Compared with the control level, MAPK activity of the VSMCs was up-regulated by 238% by treatment with angiotensin II alone which, however, did not inhibit p27 expression or induce VSMC proliferation. Costimulation with angiotensin II and PMA slightly inhibited p27 expression but VSMC proliferation was still not observed.


CONCLUSIONS
MAPK pathway is an important channel for extracellular proliferative and hypertrophic signal transduction into the nucleus of VSMCs.
Liu
Yu
Y
Department of Cardiology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
Xu
Ding-Li
DL
Wang
Ming-Hui
MH
Ouyang
Ping
P
Lai
Wen-Yan
WY
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D000804:Angiotensin II; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases