Abstract 19645: Cardiac Effects of Physiological Hypertrophy in a Murine Model of Calcium Channel Overexpression
Background — The L-type calcium channel (LTCC) is integral for calcium entrance into the cardiomyocyte to induce CICR from the SR. We have developed a mouse model with inducible, cardiac-specific expression of the β2a subunit of the LTCC (β2a), leading to pathological hypertrophy akin to post-MI heart failure. Chronic exercise is known to cause physiological hypertrophy in normal hearts, leading to enhanced contractile state and thickened heart tissue, without a pathological phenotype. We administered chronic physiological hypertrophy in the form of swim training on the β2a line and its WT counterpart, analyzing the cardiac changes.
Methods and Results — β2a (n=8) and WT (n=16) FVB mice aged 4 months were swam twice a day, four hours apart, for 21 days. They swam for 10min sessions on Day 1, with each subsequent day increasing the session time by 10 min until 90min sessions were reached. ECHO was performed at beginning and end of swim training, then terminal HW/BW ratio was determined. EF and FS increased significantly with swimming in WT (EF [%] pre-swim: 57.21±2.02 vs. post-swim: 69.98±2.88; FS [%] pre-swim: 29.53±1.34 vs. post-swim: 39.27±2.42) and from sedentary counterparts. β2a mice showed no significant change after swimming (EF [%] pre-swim: 69.8±1.75 vs. post-swim: 74.06±2.72; FS [%] pre-swim: 38.24±2.38 vs. post-swim: 42.40±2.22) and no change from sedentary β2a mice. Both ECHO parameters were significantly greater in β2a mice versus WT before swimming, but not after. There was a significant difference in HW/BW ratio in WT exercised mice versus sedentary (HW/BW [mg/g] swim: 4.63±0.2 vs. sed: 5.75±0.19) that was not present in exercised versus sedentary β2a mice (HW/BW [mg/g] swim: 5.98±0.31 vs. sed: 5.96±0.25).
Conclusions — Chronic exercise may not affect mice with pathological hypertrophy through overexpressed LTCC but causes physiological hypertrophy in their wild type counterparts.
- © 2012 by American Heart Association, Inc.