DOWN-REGULATION 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 d uring 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 p rogressively with time without significant differences in body weight or right ventricle weight-to-body weight ratio. Atrial natriuretic fac tor 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 decreas ed significantly by 58% (P < 0.03) and 40% (P < 0.05) at day 7, respec tively. p21 and p27 protein expression decreased significantly from da ys 3 to 21 in AC versus SH, concomitant with LV adaptive growth. Immun ocytochemistry 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.