Abstract 367: Exercising Exacerbates the Hypertrophic Response of Female Transgenic Mice Expressing Elevated Myocardial Na+/H+ Exchanger Isoform 1
Cardiac hypertrophy (CH) is heart growth in response to environmental demands, and a variety of hormonal, paracrine and autocrine stimuli. It is a means to reduce stress on the ventricular wall. The Na+/H+ exchanger isoform 1 (NHE1) has been implicated in the development and progression of CH. To better understand the involvement of NHE1, male and female transgenic mice that express cardiac specific active NHE1 expression were studied. N-line mice expressed wild-type NHE1, and K-line mice expressed activated NHE1. NHE activity of adult ventricular cardiomyocytes and protein expression were elevated by approximately 2 and 3-fold in the N- and K-line mice vs. control. The K-line female mice assessed by echocardiography demonstrated significant global cardiac dysfunction. Left ventricular fractional cell shortening and ejection fraction were significantly decreased in the K-line mice (23.1 ± 3.8% and 45.2 ± 6.9% K-line vs. 36.5 ± 1.1% and 66.4 ± 1.5% control, respectively; p<0.05). The K-line female mice also exhibit myocardial remodeling. The heart weight to body weight ratio was significantly greater in the K-line mice (143 ± 10.0% of control; P<0.05). Cross sectional area (K-line 195.6 ± 16.4% of control; p<0.05) and interstitial fibrosis (K-line: 275.4 ± 11.6% of control; p<0.05) were also elevated. Increased expression of active NHE1 protein in male mice was also much more detrimental than expression of the wild type protein as was seen with the female transgenic mice. Therefore, the NHE1 induced hypertrophic effect was not gender dependent. However, NHE1 expression induced gender specific differences with exercise. Exercising exaggerated the HW/BW ratio in female mice expressing activated NHE1 compared to males. These results suggest that gender specific activation of NHE1 may be critical in promoting hypertrophy in females in comparison with males.
- © 2012 by American Heart Association, Inc.