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 (AC(1) group; n = 20) or 2 mo (AC(2); n = 24) after aortic ligature. Then subgroups of AC(1) and AC(2) 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 (alpha-SKA), alpha-cardiac actin (alpha-CA), and alpha-smooth muscle actin (alpha-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 AC(2) rats at both organ and cellular levels. Conversely, AC(1) rats exhibited enhanced LV contractility and preserved cellular contractile behavior associated with increased calcium transients. Alpha-SKA expression was upregulated (+60%) in AC(1). In AC(2) ventricles, prolonged hypertension also induced a significant increase in alpha-SMA expression, mainly at the level of arterial vessels. No significant differences among groups were observed in alpha-CA expression. Our findings suggest that alpha-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.
Berni
Roberta
R
Dept. of Evolutionary and Functional Biology, Physiology Section, Univ. of Parma, V. le G. P. Usberti 11/A, I-43100, Italy.
Savi
Monia
M
Bocchi
Leonardo
L
Delucchi
Francesca
F
Musso
Ezio
E
Chaponnier
Christine
C
Gabbiani
Giulio
G
Clement
Sophie
S
Stilli
Donatella
D
D000199:Actins / Q000378:metabolism*; D000222:Adaptation, Physiological; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D020013:Calcium Signaling; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism*; D004195:Disease Models, Animal; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left
D000199:Actins; D020033:Protein Isoforms; C498862:Acta2 protein, rat