Role of G1 phase cyclins and cyclin-dependent kinases during cardiomyocyte hypertrophic growth in rats.
Cell cycle regulatory molecules are implicated in cardiomyocyte hypertrophy. We have investigated protein expression of cyclins A, D1-3, and E and cyclin-dependent kinases (CDKs) 2, 4, 5, and 6 in left ventricular (LV) tissues during the development of LV hypertrophy in rats following aortic constriction (AC). Compared with their expression in sham-operated controls (SH), expression of cyclins D2 and D3 and of CDK4 and CDK6 increased significantly from day 3 to day 21 after AC concomitant with increased LV mass. However, no significant difference was observed for CDK2 or CDK5. Cyclins A, D1, and E were undetectable. In vitro kinase activities of CDK4 and CDK6 increased approximately 70% from day 7 to day 14 in AC myocytes compared with SH myocytes (P < 0.03). Fluorescence-activated cell sorter analysis revealed a G0/G1 to G2/M phase progression in AC myocyte nuclei (22.0 +/- 1.1% in G2/M) by day 7 postoperation compared with progression in SH myocyte nuclei (14.0 +/- 0.8% in G2/M; P < 0.01). Thus an upregulation of certain cell cycle regulators is associated with cardiomyocyte hypertrophy.
Cardiovascular Cellular and Molecular Biology, Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
J M
JM
Li
R A
RA
Poolman
G
G
Brooks
D016475:3T3 Cells; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D056742:Cyclin D2; D056743:Cyclin D3; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D007163:Immunosorbent Techniques; D008297:Male; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase / Q000502:physiology; D014661:Vasoconstriction
C486196:Ccnd2 protein, mouse; C486197:Ccnd2 protein, rat; C534697:Ccnd3 protein, mouse; C534698:Ccnd3 protein, rat; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; C495902:Cdk4 protein, mouse; C495903:Cdk4 protein, rat; C495912:Cdk6 protein, mouse; C495913:Cdk6 protein, rat; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases