Li J M, Poolman R A, Brooks G
Cardiovascular Cellular and Molecular Biology, Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
Am J Physiol. 1998 Sep;275(3):H814-22. doi: 10.1152/ajpheart.1998.275.3.H814.
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.
细胞周期调节分子与心肌细胞肥大有关。我们研究了在大鼠主动脉缩窄（AC）后左心室（LV）肥厚发展过程中，左心室组织中细胞周期蛋白A、D1 - 3和E以及细胞周期蛋白依赖性激酶（CDK）2、4、5和6的蛋白表达。与假手术对照组（SH）相比，AC术后第3天至第21天，细胞周期蛋白D2和D3以及CDK4和CDK6的表达随着左心室质量增加而显著增加。然而，CDK2或CDK5未观察到显著差异。细胞周期蛋白A、D1和E未检测到。与SH心肌细胞相比，AC心肌细胞中CDK4和CDK6的体外激酶活性在术后第7天至第14天增加了约70%（P < 0.03）。荧光激活细胞分选分析显示，术后第7天，AC心肌细胞核从G0/G1期向G2/M期进展（G2/M期为22.0 +/- 1.1%），而SH心肌细胞核进展为（G2/M期为14.0 +/- 0.8%；P < 0.01）。因此，某些细胞周期调节因子的上调与心肌细胞肥大相关。
