title: Correlation of alpha-skeletal actin expression, ventricular fibrosis and heart function with the degree of pressure overload cardiac hypertrophy in rats.
abstract: We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, and invasive haemodynamic measurements were performed in anaesthetized animals. After killing, subgroups of AC and C rats were used to evaluate in the left ventricle the expression and spatial distribution of alpha-skeletal actin and the amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic pressure, ventricular weight and ventricular wall thickness. AC0.7 and AC0.4 rats also showed a larger amount of fibrosis and upregulation of alpha-skeletal actin expression associated with a higher vulnerability to ventricular arrhythmias (AC0.7 and AC0.4) and enhanced myocardial contractility (AC0.4). Our results illustrate the progressive changes in the extracellular matrix features accompanying early ventricular remodelling in response to different degrees of pressure overload that may be involved in the development of cardiac electrical instability. We also demonstrate for the first time a linear correlation between an increase in alpha-skeletal actin expression and the degree of compensated cardiac hypertrophy, possibly acting as an early compensatory mechanism to maintain normal mechanical performance.
authors.affiliation: Dipartimento di Biologia Evolutiva e Funzionale-Sezione Fisiologia, Università di Parma, Parco Area delle Scienze 11A, 43100, Parma, Italy. donatella.stilli@unipr.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Stilli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bocchi
authors.forename: Roberta
authors.initials: R
authors.lastname: Berni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Zaniboni
authors.forename: Francesca
authors.initials: F
authors.lastname: Cacciani
authors.forename: Christine
authors.initials: C
authors.lastname: Chaponnier
authors.forename: Ezio
authors.initials: E
authors.lastname: Musso
authors.forename: Giulio
authors.initials: G
authors.lastname: Gabbiani
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006339:Heart Rate; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013223:Statistics as Topic; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000199:Actins