Abstract 1226: Augmentation Of Cardiac Function In Response To Pressure Overload In Transgenic Mice With A Cardiac-Specific Expression Of Adenylyl Cyclase Type 2
The results from studies examining the effects of transgenic (TG) mice with overexpression of the major adenylyl cyclase (AC) isoforms in the heart, AC5 and 6, has been controversial. Accordingly, we examined the effects of a non-calcium regulated AC isoform, AC2, by overexpressing it in the heart. This resulted in a 3 fold increase in overall cardiac AC activity. Baseline left ventricular ejection fraction (LVEF), measured by echocardiography, was higher (P<0.05) in TG mice when compared to WT (75±1% vs 72±1%) while heart rate was similar (P<0.05). The extent of increased LVEF stimulated by isoproterenol (ISO) was also higher in TG suggesting an increase in functional response of beta-AR signaling in these transgenic mice. Aortic banding for 1 wk induced significantly greater (P<0.05) LV hypertrophy in TG compared to WT as indicated by LV weight (LVW)/tibial length (TL) ratio (7.1±0.4 vs 6.0±0.3 mg/mm, P<0.05). Aortic banding resulted in no change of LVEF in the AC2TG (76±3%) or in WT (70±3%), i.e., LV function was maintained. Pathological examination of the 1wk banded hearts demonstrated fewer TUNEL positive myocytes in the AC2TG (0.16±0.08 cells/microm2) vs WT (1.00±0013 cell/microm2) (P<0.05). Cross-sectional myocyte area in AC2TG was also larger (316±16microm2) than WT (289±20microm2) which confirmed the increased in LV/TL. Thus, a moderate level of AC2 overexpression in the heart increases the amount of cardiac hypertrophy, in response to pressure overload, but exerts a beneficial effect on apoptosis and LV function.