Modulation of actin isoform expression before the transition from experimental compensated pressure-overload cardiac hypertrophy to decompensation.

In a rat model of long-lasting pressure-overload hypertrophy, we investigated whether changes in the relative expression of myocardial actin isoforms are among the early signs of ventricular mechanical dysfunction before the transition toward decompensation. Forty-four rats with infrarenal aortic banding (AC rats) were studied. Hemodynamic parameters were measured 1 mo (AC1 group; n = 20) or 2 mo (AC2; n = 24) after aortic ligature. Then subgroups of AC1 and AC2 left ventricles (LV) were used to evaluate 1) LV anatomy and fibrosis (morphometry), 2) expression levels (immunoblotting) and spatial distribution (immunohistochemistry) of alpha-skeletal actin (α-SKA), alpha-cardiac actin (α-CA), and alpha-smooth muscle actin (α-SMA), and 3) cell mechanics and calcium transients in enzimatically isolated myocytes. Although the two AC groups exhibited a comparable degree of hypertrophy (+30% in LV mass; +20% in myocyte surface) and a similar increase in the amount of fibrosis compared with control animals (C group; n = 22), a worsening of LV mechanical performance was observed only in AC2 rats at both organ and cellular levels. Conversely, AC1 rats exhibited enhanced LV contractility and preserved cellular contractile behavior associated with increased calcium transients. Alpha-SKA expression was upregulated (+60%) in AC1. In AC2 ventricles, prolonged hypertension also induced a significant increase in α-SMA expression, mainly at the level of arterial vessels. No significant differences among groups were observed in α-CA expression. Our findings suggest that α-SKA expression regulation and wall remodeling of coronary arterioles participate in the development of impaired kinetics of contraction and relaxation in prolonged hypertension before the occurrence of marked histopathologic changes.