Abstract 341: Both Beta-1 and Beta-2 Adrenergic Receptors (ARs) are Required for Pressure Overload Cardiac Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Mingming Zhao ◽  
Roger Wagner ◽  
Giovanni Fajardo ◽  
Takashi Urashima ◽  
Sara Farahani ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Kinase Inhibitor ◽  
Binding Protein ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Heart Weight ◽  
Lv Function ◽  
List Type ◽  
Hypertrophic Response ◽  
Calgranulin B

In isolated myocytes, hypertrophy induced by norepinephrine is mediated via β-ARs, however, in vivo, mice with deletions of both major cardiac β-ARs still develop hypertrophy with pressure overload. The mechanism by which the heart adapts to pressure overload, producing either adaptive or maladaptive remodeling is still not completely understood. To study the role of β-ARs in pressure overload hypertrophy, we performed transverse aortic constriction (TAC) in congenic mice with targeted deletions of β1, β2 and both β1 and β2-ARs and in sham controls. After 3 wks, β1−/− mice showed a 21% increase in heart weight to body weight ratio (HW/BW) vs. sham, similar to WT (HW/BW 5.02 ± 0.72 for β1−/− vs. 5.20 ± 0.92 for WT). β2−/− mice showed an exaggerated (49%) hypertrophic response (HW/BW 5.81 ± 0.53, p < 0.001 vs. WT). Only when both β-ARs were ablated was hypertrophy fully attenuated: in β1β2−/− mice HW/BW increased only 8% (HW/BW 4.30 ± 0.31, p < 0.01 vs. WT). Echocardiography showed that peak band gradient was not different between groups (WT 45.3 ± 4.1, β1−/− 47.2 ± 10.2, β2−/− 49.0 ± 9.7, β1β2−/− 53.2 ± 11.3 mmHg) and all groups maintained normal LV function. Morphometric analysis confirmed the absence of hypertrophy in the β1β2−/−: mean cross-sectional area for WT was 254.7 ± 34.9 vs. β1β2−/− 115.8 ± 16.7μm 2 , which was not different from sham. Gene microarray analysis detected a set of genes which were differentially expressed in β1β2−/− vs. WT, β1−/−, or β2−/−: S100 calcium binding protein A9/calgranulin B (S100a9, 4.5-fold up); Cyclin-dependent kinase inhibitor 1A/P21 (Cdkn1a, 3.8-fold up); Metallothioneins Mt1 (3-fold up) and Mt2 (2.7-fold up); FK506 binding protein 5, a glucocorticoid receptor-regulating co-chaperone and calcineurin inhibitor (3.2-fold up). In contrast, TGFβ2 was upregulated in WT, β1−/− and β2−/− but not in β1β2−/−. Differentially regulated genes were validated by SYBR QRT-PCR on the same RNA samples. Thus, β2-AR signaling may serve to limit the hypertrophic response to pressure afterload. However, both β-ARs are required for the development of a normal hypertrophic response. Ablation of both β-AR subtypes alters expression of several genes, some of which may be critical to the hypertrophic program.

Abstract 241: Cardiac-Specific Overexpression of Runx2 Mediates Cardiac Hypertrophy and Dysfunction in Mice

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hiroyuki Nakayama ◽  
Tatsuto Hamatani ◽  
Shohei Kumagai ◽  
Kota Tonegawa ◽  
Tomomi Yamashita ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Premature Death ◽  
Heart Weight ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Hypertrophic Response ◽  
Neonatal Cardiomyocytes

Backgrounds: Recent studies demonstrated that the osteopontin (OPN), an acid phosphoprotein plays pivotal roles in cardiac hypertrophy and failure. An osteogenic transcription factor Runx2 regulates the expression of OPN in osteoblasts. In the present study, we examined the pathological role of Runx2 in cardiac hypertrophy and failure. Methods and Results: Runx2 expression was detected in neonatal cardiomyocytes and upregulated in heart 14 days after myocardial infarction (MI) as well as 7days after transverse aortic constriction (TAC) procedures. To determine the functional role of Runx2 in heart, we generated transgenic mice (TG) with inducible cardiac-specific overexpression of Runx2. Two TG lines (low and high) were obtained and high-expressing TG (HE-TG) showed premature death within 8 weeks of age specifically in male mice. At two months of age, the survived male and female HE-TG displayed significant increases in heart weight/body weight ratio (mg/g) compared to controls (control; 4.95±0.26, n=6 vs HE-TG; 6.63±0.12, n=5, p<.05). Consistent with those results, the expression of hypertrophic marker genes such as atrial natriuretic factor (ANF) and αskeletal actin significantly increased in HE-TG heart assessed by real-time RT-PCR analysis. In addition, HE-TG mice demonstrated decreased fractional shortening assessed by echocardiography (control; 44.1±1.89%, n=9 vs HE-TG; 23.9±3.48%, n=7, p<.05). HE-TG mice demonstrated significantly lower heart rate (control; 630±18 bpm, vs HE-TG; 350±74 bpm, n=3 each, p<.05) and complete atrioventricular block by telemetry analysis. In response to pressure overload, low expressing TG (LE-TG) demonstrated higher mortality and enhanced cardiac hypertrophic response after TAC (control; 6.20±0.23, n=6 vs LE-TG; 6.90±0.26, n=4, p<.05). Conclusions: Targeted expression of Runx2 in heart mediates cardiac dysfunction and hypertrophy in mice. Thus, Runx2 could be a novel therapeutic target for heart failure.

Abstract 1876: Functional Effect of Chronic Urotensin II Receptor Antagonist on L-Type Ca 2+ Current in Mouse Model of Progressive Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Peng Zhou ◽  
Heng-Jie Cheng ◽  
Michael Cross ◽  
Michael F Callahan ◽  
Bridget Brosnihan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Receptor Antagonist ◽  
Weight Ratio ◽  
Heart Association ◽  
Cell Voltage ◽  
Fold Increase ◽  
Left Ventricular ◽  
Lv Function ◽  
List Type ◽  
Urotensin Ii

Voltage-gated Ca 2+ channels play fundamental roles in the regulation of cardiac function by various neurotransmitters. Recently, we have shown that urotensin II (UII), a potent vasoconstrictor, inhibits L-type Ca 2+ current (I Ca,L ) and produces negative inotropic action. In heart failure (HF), the UII-mediated pathway is upregulated, suggesting a therapeutic value of UII receptor antagonist (UII-ANT) for HF. However, the role and mechanism of chronic UII-ANT in HF is unclear. We tested the hypothesis that chronic UII-ANT may improve cardiac I Ca,L , preventing β-adrenergic deregulation on I Ca,L and limit HF progression. We examined plasma levels of norepinephrine (NE), left ventricular (LV) function, and myocyte I Ca,L responses to isoproterenol (ISO) in 3 age-matched groups of mice: HF (n = 7), 2 months after ISO (150 mg/kg sq for 2 days); HF/UII-ANT (n = 11), 1 month after receiving ISO, then urantide, a potent UII-ANT (10 −5 M/kg/day, sq via implanted osmotic mini pump), given for 1 month; and Controls (n = 7). I Ca,L was measured using whole-cell voltage clamp technique. Compared with controls, ISO-treated mice progressed to HF with 4.7-fold increase in plasma NE (18975 vs 4066 pg/ml) and LV dilatation associated with increased myocyte length (ML, 155 vs120 μm) and heart-to-body weight ratio (H/BW, 7.6 vs 5.5 g/kg). Stroke volume (SV, 30.3 vs 61.4 μl) and ejection fraction (EF, 39% vs 60%) were decreased. Compared with normal myocytes, in HF myocytes, I Ca,L was reduced (50%, 3.7 ± 0.2 vs 7.4 ± 0.2 pA/pF), and I Ca,L response to β-AR stimulation (ISO, 10 −8 M) was attenuated (11% vs 35%) (p < 0.01). In HF/UII-ANT mice, plasma NE (5148 pg/ml), SV (57.9 μl), and EF (57%) returned close to control levels with retained normal ML (124 μm) and H/BW (5.9 g/kg). Moreover, compared with controls, in HF/UII-ANT mice, ISO caused similar increases in the peak I Ca,L (32% vs 35%). Chronic UII-ANT treatment normalizes LV L-type Ca 2+ channel basal function and β-adrenergic regulation, leading to regression of LV and myocyte dysfunction and remodeling in mice with ISO-induced HF. This research has received full or partial funding support from the American Heart Association, AHA National Center.

scholarly journals Astrocytic modulation of information processing by layer 5 pyramidal neurons of the mouse visual cortex

2020 ◽  
Author(s):  
Dimitri Ryczko ◽  
Maroua Hanini-Daoud ◽  
Steven Condamine ◽  
Benjamin J. B. Bréant ◽  
Maxime Fougère ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Binding Protein ◽  
Contextual Information ◽  
Dendritic Tree ◽  
Cortical Layer ◽  
List Type ◽  
Ionic Environment

AbstractThe most complex cerebral functions are performed by the cortex which most important output is carried out by its layer 5 pyramidal neurons. Their firing reflects integration of sensory and contextual information that they receive. There is evidence that astrocytes influence cortical neurons firing through the release of gliotransmitters such as ATP, glutamate or GABA. These effects were described at the network and at the synaptic levels, but it is still unclear how astrocytes influence neurons input-output transfer function at the cellular level. Here, we used optogenetic tools coupled with electrophysiological, imaging and anatomical approaches to test whether and how astrocytic activation affected processing and integration of distal inputs to layer 5 pyramidal neurons (L5PN). We show that optogenetic activation of astrocytes near L5PN cell body prolonged firing induced by distal inputs to L5PN and potentiated their ability to trigger spikes. The observed astrocytic effects on L5PN firing involved glutamatergic transmission to some extent but relied on release of S100β, an astrocytic Ca2+-binding protein that decreases extracellular Ca2+ once released. This astrocyte-evoked decrease of extracellular Ca2+ elicited firing mediated by activation of Nav1.6 channels. Our findings suggest that astrocytes contribute to the cortical fundamental computational operations by controlling the extracellular ionic environment.Key Points SummaryIntegration of inputs along the dendritic tree of layer 5 pyramidal neurons is an essential operation as these cells represent the most important output carrier of the cerebral cortex. However, the contribution of astrocytes, a type of glial cell to these operations is poorly documented.Here we found that optogenetic activation of astrocytes in the vicinity of layer 5 in the mouse primary visual cortex induce spiking in local pyramidal neurons through Nav1.6 ion channels and prolongs the responses elicited in these neurons by stimulation of their distal inputs in cortical layer 1.This effect partially involved glutamatergic signalling but relied mostly on the astrocytic calcium-binding protein S100β, which regulates the concentration of calcium in the extracellular space around neurons.These findings show that astrocytes contribute to the fundamental computational operations of the cortex by acting on the ionic environment of neurons.

scholarly journals PKC-β is not necessary for cardiac hypertrophy

2001 ◽  
Vol 280 (5) ◽  
pp. H2264-H2270 ◽  
Author(s):  
Brian B. Roman ◽  
David L. Geenen ◽  
Michael Leitges ◽  
Peter M. Buttrick
Keyword(s):  
Cardiac Hypertrophy ◽  
Gene Knockout ◽  
Weight Ratio ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Hypertrophic Response ◽  
Pathological Hypertrophy ◽  
Pkc Β ◽  
And Control

Studies in human and rodent models have shown that activation of protein kinase C-β (PKC-β) is associated with the development of pathological hypertrophy, suggesting that ablation of the PKC-β pathway might prevent or reverse cardiac hypertrophy. To explore this, we studied mice with targeted disruption of the PKC-β gene (knockout, KO). There were no detectable differences in expression or distribution of other PKC isoforms between the KO and control hearts as determined by Western blot analysis. Baseline hemodynamics were measured using a closed-chest preparation and there were no differences in heart rate and arterial or left ventricular pressure. Mice were subjected to two independent hypertrophic stimuli: phenylephrine (Phe) at 20 mg · kg−1 · day−1 sq infusion for 3 days, and aortic banding (AoB) for 7 days. KO animals demonstrated an increase in heart weight-to-body weight ratio (Phe, 4.3 ± 0.6 to 6.1 ± 0.4; AoB, 4.0 ± 0.1 to 5.8 ± 0.7) as well as ventricular upregulation of atrial natriuretic factor mRNA analogous to those seen in control animals. These results demonstrate that PKC-β expression is not necessary for the development of cardiac hypertrophy nor does its absence attenuate the hypertrophic response.

scholarly journals Low-intensity aerobic interval training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine

2010 ◽  
Vol 299 (5) ◽  
pp. H1348-H1356 ◽  
Author(s):  
Craig A. Emter ◽  
Christopher P. Baines
Keyword(s):  
Body Weight ◽  
Exercise Training ◽  
Mitochondrial Dysfunction ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Lv Function ◽  
Body Weight Ratio ◽  
Miniature Swine ◽  
Low Intensity

Cardiac hypertrophy in response to hypertension or myocardial infarction is a pathological indicator associated with heart failure (HF). A central component of the remodeling process is the loss of cardiomyocytes via cell death pathways regulated by the mitochondrion. Recent evidence has indicated that exercise training can attenuate or reverse pathological remodeling, creating a physiological phenotype. The purpose of this study was to examine left ventricular (LV) function, remodeling, and cardiomyocyte mitochondrial function in aortic-banded (AB) sedentary (HFSED; n = 6), AB exercise-trained (HFTR, n = 5), and control sedentary ( n = 5) male Yucatan miniature swine. LV hypertrophy was present in both AB groups before the start of training, as indicated by increases in LV end-diastolic volume, LV end-systolic volume (LVESV), and LV end-systolic dimension (LVESD). Exercise training (15 wk) prevented further increases in LVESV and LVESD ( P < 0.05). The heart weight-to-body weight ratio, LV + septum-to-body weight ratio, LV + septum-to-right ventricle ratio, and cardiomyocyte cross-sectional area were increased in both AB groups postmortem regardless of training status. Preservation of LV function after exercise training, as indicated by the maintenance of fractional shortening, ejection fraction, and mean wall shortening and increased stroke volume, was associated with an attenuation of the increased LV fibrosis (23%) and collagen (36%) observed in HFSED animals. LV mitochondrial dysfunction, as measured by Ca2+-induced mitochondrial permeability transition, was increased in HFSED ( P < 0.05) but not HFTR animals. In conclusion, low-intensity interval exercise training preserved LV function as exemplified by an attenuation of fibrosis, maintenance of a positive inotropic state, and inhibition of mitochondrial dysfunction, providing further evidence of the therapeutic potential of exercise in a clinical setting.

scholarly journals Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy

2014 ◽  
Vol 307 (5) ◽  
pp. H752-H761 ◽  
Author(s):  
William M. Yarbrough ◽  
Catalin Baicu ◽  
Rupak Mukherjee ◽  
An Van Laer ◽  
William T. Rivers ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Left Ventricular ◽  
Lv Function ◽  
Type I ◽  
Matrix Remodeling ◽  
Protective Effects ◽  
Ecm Remodeling ◽  
Hypertrophic Response ◽  
Lv Mass ◽  
And Function

Historically, the tissue inhibitors of matrix metalloproteinases (TIMPs) were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular (LV) dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac-specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice (3.5 ± 0.1 mo of age, equal sex distribution) with TIMP-4OE ( n = 38), TIMP-4KO ( n = 24), as well as age/strain-matched wild type (WT, n = 25), whereby indexes of LV remodeling and function such as LV mass and ejection fraction (LVEF) were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was ∼25% lower in the TIMP-4KO group ( P < 0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (48 ± 2% and 45 ± 3%, respectively) but was higher with TIMP-4OE (57 ± 2%, P < 0.05). With LVPO, LV myocardial collagen expression (type I, III) increased by threefold in all groups ( P < 0.05), but surprisingly this response was most robust in the TIMP-4KO group. These unique findings suggest that increased myocardial TIMP-4 in the context of a LVPO stimulus may actually provide protective effects with respect to survival, LV function, and extracellular matrix (ECM) remodeling. These findings challenge the canonical belief that increased levels of specific myocardial TIMPs, such as TIMP-4 in and of themselves, contribute to adverse ECM accumulation following a pathological stimulus, such as LVPO.

scholarly journals Impacts of a Specific Cyclooxygenase-2 Inhibitor on Pressure Overload–Induced Myocardial Hypertrophy in Rats

2019 ◽  
Vol 22 (6) ◽  
pp. E432-E437
Author(s):  
Zhixiang Xie ◽  
Shuyin Wang ◽  
Zijing Liang ◽  
Liangbo Zeng ◽  
Rongde Lai ◽  
...  
Keyword(s):  
Myocardial Hypertrophy ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cyclooxygenase 2 ◽  
Inflammatory Factors ◽  
Heart Weight ◽  
Sham Operation ◽  
Surgery Group ◽  
Tnf Α

Objective: The aim of this study was to observe the impacts of the specific cyclooxygenase-2 inhibitor celecoxib on cardiac structures, functions, and inflammatory factors during the process of pressure overload–induced myocardial hypertrophy. Methods: Twenty-four male Sprague Dawley rats were randomly divided into 3 groups: the sham operation group, the surgery group, and the celecoxib group. The model was established according to the abdominal aortic coarctation method. Results: At 16 weeks, rats in the celecoxib group were fed a celecoxib-mixed diet (10 mg/kg) for 8 consecutive weeks. At week 24 after model establishment, the cardiac structures and functions were observed; changes in the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, prostaglandin E2 (PGE2), C-reactive protein (CRP), and uric acid (UA) were detected; and the contents of Smad1/2/3 proteins (Smad1, Smad2, and Smad3)  were determined. Left ventricular mass index, the heart weight/body weight ratio, and TNF-α, TGF-β, PGE2, CRP, and UA levels of the celecoxib group were all significantly decreased relative to those of the surgery group (P < .05); moreover, the cardiac functions were significantly improved compared to those of the surgery group (P < .05). Conclusions: These results show that inflammatory factors are involved in the myocardial hypertrophy process and that celecoxib may reverse myocardial hypertrophy through a variety of pathways.

Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure-overload-induced feline LV hypertrophy

1993 ◽  
Vol 265 (6) ◽  
pp. H2009-H2016 ◽  
Author(s):  
B. A. Bailey ◽  
S. R. Houser
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Time Course ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Cytosolic Calcium ◽  
Left Ventricular ◽  
Heart Weight ◽  
Body Weight Ratio ◽  
Rest Periods ◽  
Premature Beats

Alterations in Ca2+ homeostasis that involve the sarcoplasmic reticulum (SR) were studied in feline left ventricular (LV) myocytes isolated from hearts with LV hypertrophy induced by slow, progressive pressure overload. At death, severe hypertrophy was evidenced by increased heart weight-to-body weight ratio (8.4 +/- 0.6 vs. 4.2 +/- 0.2 g/kg in controls). Steady-state Ca2+ transients (measured as. indo 1 fluorescence at 410 nm/480 nm; I410/I480) in LV hypertrophy (LVH) myocytes had diminished peak amplitudes (I410/I480 2.28 +/- 0.07 vs. 2.53 +/- 0.07 in controls) and prolonged durations (0.75 +/- 0.03 vs. 0.59 +/- 0.02 s in controls). The magnitude of shortening was reduced and the contractile duration was prolonged in LVH myocytes. The idea that changes in SR function are responsible for these alterations in the Ca2+ transient was tested by studying two aspects of SR-related Ca2+ homeostasis. Restitution of releasable SR Ca2+ was studied by measuring indo 1 transients and contractions during premature beats. The time course of restitution of both the indo 1 transient and contraction of hypertrophy myocytes was significantly slower than in controls. These data suggest that restitution of releasable SR Ca2+ is slowed in hypertrophy myocytes. The reduction of the indo 1 transient and contraction in beats following long rest periods (rest decay) was measured to determine the rate of Ca2+ loss from the SR. Rest decay was significantly (P < 0.05) more pronounced in hypertrophy myocytes, suggesting that Ca2+ loss from the SR is accelerated in these myocytes. (ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ablation of Histidine-Rich Calcium Binding Protein (HRC) Results in Severe Cardiac Hypertrophy and Dysfunction in Pressure Overload Model

2012 ◽  
Vol 102 (3) ◽  
pp. 555a
Author(s):  
Chang Sik Park ◽  
Hyeseon Cha ◽  
Sora Jin ◽  
Woo Jin Park ◽  
Jung Hee Cho ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Calcium Binding ◽  
Binding Protein ◽  
Pressure Overload ◽  
Calcium Binding Protein

Abstract 367: Exercising Exacerbates the Hypertrophic Response of Female Transgenic Mice Expressing Elevated Myocardial Na + /H + Exchanger Isoform 1

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Fatima Mraiche ◽  
Larry Fliegel
Keyword(s):  
Transgenic Mice ◽  
Interstitial Fibrosis ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Wild Type ◽  
Cross Sectional ◽  
Hypertrophic Response ◽  
Female Mice ◽  
Gender Specific

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.

Sign in / Sign up

Export Citation Format

Share Document