Role of G1 phase cyclins and cyclin-dependent kinases during cardiomyocyte hypertrophic growth in rats

Cardiovascular Cellular and Molecular Biology, Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom 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 ~70% from day 7 to day 14 in AC myocytes compared with SH myocytes ( P