Abstract 1859: High Dose Atorvastatin Induces Myocardial Hypertrophy In Swine: Role Of Adiponectin And Akt
Background: The adipokine, adiponectin, as well as its downstream mediator, Akt, have been implicated in myocardial hypertrophy and are also affected in-vitro by statin therapy. In a large animal model, we examined the effects of high dose atorvastatin on myocardial hypertrophy, at the morphological and molecular level, and on adiponectin and Akt signaling.
Methods: Yucatan miniswine (7 week old) were fed either a normal diet, with (ND-ATR, n = 8) or without (ND, n = 8) atorvastatin (1.5 mg/kg/day) or a hypercholesterolemic diet, with (HC-ATR, n = 6) or without (HC, n = 6) atorvastatin (3 mg/kg/day) for 20 weeks. All animals underwent circumflex ameroid placement to induce myocardial ischemia. Gross morphologic, histologic, and molecular studies were performed 7 weeks later.
Results: Atorvastatin reduced serum cholesterol levels in HC animals (14.2 ± 1.8 vs. 20.1 ± 1.8 mmol/L, p < 0.05) and was associated with variable degrees of myocardial hypertrophy (Fig 1A⇓). Molecular markers of myocardial hypertrophy, including total actin, α-skeletal actin, fetal cardiac actin, and brain natriuretic peptide, were significantly elevated in ND-ATR and HC-ATR animals (all p < 0.01, Fig 1B⇓). Akt phosphorylation was profoundly increased (3.4 fold in ND-ATR, 4.3 fold in HC-ATR; p < 0.01). and adiponectin receptor, AdipoR2, expression was significantly reduced with atorvastatin treatment (− 21%, p = 0.03).
Conclusions: In Yucatan miniswine, high dose atorvastatin treatment was associated with morphlogic and molecular evidence of myocardial hypertrophy. Persistent Akt activation and alterations in adiponectin signaling may be responsible for atorvastatin mediated myocardial hypertrophy.