Downregulation of cyclin-dependent kinase inhibitors p21 and p27 in pressure-overload hypertrophy.
We postulated that the cyclin-dependent kinase inhibitors p21 and p27 could regulate the alterations in growth potential of cardiomyocytes during left ventricular hypertrophy (LVH). LVH was induced in adult rat hearts by aortic constriction (AC) and was monitored at days 0, 1, 3, 7, 14, 21, and 42 postoperation. Relative to sham-operated controls (SH), left ventricle (LV) weight-to-body weight ratio in AC increased progressively with time without significant differences in body weight or right ventricle weight-to-body weight ratio. Atrial natriuretic factor mRNA increased significantly in AC to 287% at day 42 compared with SH (P < 0.05), whereas p21 and p27 mRNA expression in AC rats decreased significantly by 58% (P < 0.03) and 40% (P < 0.05) at day 7, respectively. p21 and p27 protein expression decreased significantly from days 3 to 21 in AC versus SH, concomitant with LV adaptive growth. Immunocytochemistry showed p21 and p27 expression in cardiomyocyte nuclei. Thus downregulation of p21 and p27 may modulate the adaptive growth of cardiomyocytes during pressure overload-induced LVH.
Li
J M
JM
Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Brooks
G
G
D016475:3T3 Cells; D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D001835:Body Weight; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins; D014661:Vasoconstriction; D016277:Ventricular Function, Left
C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; C493961:Cdkn1b protein, mouse; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009320:Atrial Natriuretic Factor; D018844:Cyclin-Dependent Kinases