Abstract 15386: Reduction in Striated Preferentially Expressed Gene leads to Decompensated Heart Failure after Transverse Aortic Constriction in Mice
Introduction: Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family of proteins. Disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy and pervasive death shortly after birth on a C57BL/6 background, and occasional survival on a C57/BL/6 x 129 SvJ background.
Hypothesis: Beyond the neonatal period, Speg also plays an important role in adult heart function.
Methods: 1) To characterize adult mice, we bred Speg heterozygous (+/-) mice (C57BL/6 x 129SvJ), and performed echocardiograms (echos) on surviving Speg homozygous (-/-) mice at 10 weeks of age. 2) 8 week old wild-type (Speg+/+) and Speg+/- mice (C57BL/6) underwent transverse aortic constriction (TAC), and echos were performed at 2 and 4 weeks post-TAC.
Results: 1) Adult Speg-/- mice (C57BL/6 x 129SvJ) showed a significant increase in ratio of heart to body weight when compared with Speg+/+ and Speg+/- hearts (7.57±0.34 mg/gm versus 4.42±0.25 and 4.12±0.08 mg/gm, respectively). Both ejection fraction (EF) and fractional shortening (FS) were significantly decreased in Speg-/- hearts (46.7±10.9% and 24.3±6.2%, respectively), compared with Speg+/+ (84.4±7.2% and 52.3±2.6%) and Speg+/- (77.2±1.6% and 44.9±1.7%) hearts. 2) There was no significant difference between heart weight and function of Speg+/+ and Speg+/- mice (C57BL/6) at baseline, and both groups showed a significant increase in heart weight at 2 and 4 weeks after TAC. LV internal diameter (LVID) decreased in both groups at 2 weeks after TAC. However, by 4 weeks post-TAC, LVID increased significantly in Speg+/- mice compared with sham mice, and Speg+/+ mice receiving TAC of the same duration. Cardiac function was initially preserved in both groups after 2 weeks of TAC, however at 4 weeks the EF and FS more dramatically decreased in the Speg+/- (39.8±3.5% and 19.6±2.0%, respectively) compared with Speg+/+ (56.3±4.3% and 30.5±3.4%) mice.
Conclusions: 1) Speg-/- mice (C57BL/6 x 129SvJ) that survive to adulthood develop severe cardiac dysfunction. 2) After 4 weeks of pressure overload, the Speg+/- hearts decompensated, with a greater increase in LV chamber size and a more marked decrease in function, compared with Speg+/+ hearts. Thus, Speg expression is important for adult heart function.
Author Disclosures: X. Liu: None. M.A. Perrella: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.