Cardiac hypertrophy in the ferret increases expression of the Na(+)-K(+)-ATPase alpha 1- but not alpha 3-isoform

1994 ◽  
Vol 266 (3) ◽  
pp. H1221-H1227 ◽  
Author(s):  
C. B. Book ◽  
R. P. Wilson ◽  
Y. C. Ng
Keyword(s):  
Cardiac Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Northern Blotting ◽  
Myosin Heavy Chain Isoforms ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Morphometric Measurements ◽  
Abdominal Aortic ◽  
Ferret Heart

Work overload alters expression of the Na(+)-K(+)-adenosinetriphosphatase (ATPase) multigene family in the myocardium. However, due to lack of an appropriate animal model, very little is known regarding regulation of the alpha 3-isoform. We previously reported that adult ferret myocardium expresses the alpha 1- and alpha 3-isoforms of Na(+)-K(+)-ATPase. In the current study we examined the relative abundances of these isoforms in a recently developed ferret model of pressure-overload cardiac hypertrophy. Ferrets with abdominal aortic constriction (Coarc) developed significant left ventricular hypertrophy based on altered morphometric measurements and switching of the myosin heavy chain isoforms. Western and Northern blotting analyses showed that in hypertrophied left ventricles of Coarc ferrets the abundance of alpha 1-protein increased (27%), whereas that of alpha 1-mRNA remained unchanged. In nonhypertrophied right ventricles of Coarc ferrets abundance of alpha 1-protein remained unchanged. Expression of the alpha 3-isoform in left ventricles of Coarc ferrets remained unchanged at both protein and mRNA levels. By contrast, abundance of beta 1-mRNA increased significantly (31%), whereas beta 1-protein remained unchanged. Na(+)-K(+)-ATPase activity, estimated by K(+)-dependent nitrophenyl phosphatase activity, did not differ between left ventricular homogenates from Coarc and sham-operated ferrets. In conclusion, these studies indicate that in hypertrophied ferret heart Na(+)-K(+)-ATPase isoforms are differentially regulated at pretranslational, as well as at translational-posttranslational levels.

Abstract 313: STIM1 Silencing Reverses Pressure-overload Induced Cardiac Hypertrophy In Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ludovic O Bénard ◽  
Daniel S Matasic ◽  
Mathilde Keck ◽  
Anne-Marie Lompré ◽  
Roger J Hajjar ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Aortic Banding ◽  
Cross Section Area ◽  
Abdominal Aortic ◽  
Section Area

STromal Interaction Molecule 1 (STIM1), a membrane protein of the sarcoplasmic reticulum, has recently been proposed as a positive regulator of cardiomyocyte growth by promoting Ca2+ entry through the plasma membrane and the activation of Ca2+-mediated signaling pathways. We demonstrated that STIM1 silencing prevented the development of left ventricular hypertrophy (LVH) in rats after abdominal aortic banding. Our aim was to study the role of STIM1 during the transition from LVH to heart failure (HF). For experimental timeline, see figure. Transverse Aortic Constriction (TAC) was performed in C57Bl/6 mice. In vivo gene silencing was performed using recombinant Associated AdenoVirus 9 (AAV9). Mice were injected with saline or with AAV9 expressing shRNA control or against STIM1 (shSTIM1) (dose: 1e+11 viral genome), which decreased STIM1 cardiac expression by 70% compared to control. While cardiac parameters were similar between the TAC groups at weeks 3 and 6, shSTIM1 animals displayed a progressive and total reversion of LVH with LV walls thickness returning to values observed in sham mice at week 8. This reversion was associated with the development of significant LV dilation and severe contractile dysfunction, as assessed by echography. Hemodynamic analysis confirmed the altered contractile function and dilation of shSTIM1 animals. Immunohistochemistry showed a trend to more fibrosis. Despite hypertrophic stimuli, there was a significant reduction in cardiac myocytes cross-section area in shSTIM1-treated animals as compared to other TAC mice. This study showed that STIM1 is essential to maintain compensatory LVH and that its silencing accelerates the transition to HF.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

Altered renal dopamine receptors during development of cardiac hypertrophy

1992 ◽  
Vol 262 (5) ◽  
pp. E569-E573
Author(s):  
P. K. Ganguly ◽  
K. Mukherjee ◽  
Y. Chen
Keyword(s):  
Cardiac Hypertrophy ◽  
Dopamine Receptors ◽  
Pressure Overload ◽  
Total Body Weight ◽  
Left Ventricular ◽  
Kidney Cortex ◽  
Sprague Dawley ◽  
Aortic Constriction ◽  
Compensatory Response ◽  
Abdominal Aortic

The characteristics of dopamine receptors were studied in heart and kidney using the radiolabeled receptor assay of [3H]spiperone during the development of cardiac hypertrophy. Male Sprague-Dawley rats (175-200 g) underwent abdominal aortic constriction above the renal arteries and were studied 3, 14, and 28 days thereafter. Sham-operated animals without aortic constriction were used as control. Although the ratio of left ventricular weight to total body weight was significantly increased 14 and 28 days after aortic constriction in animals, [3H]spiperone binding in left ventricular membrane was increased as early as 3 days after aortic constriction. At 14 days, the binding was still elevated and, by 28 days, it returned to control values. In contrast, membranes obtained from kidney cortex showed an elevation of [3H]spiperone binding only at 28 days after aortic constriction; at 3 days the binding values were decreased. A reciprocal correlation was found between the number of dopamine receptors and the activity of Na(+)-K(+)-ATPase at 28 days of aortic constriction; the enzyme activity, as measured by the release of 32Pi from [gamma-32P]ATP, was decreased in kidney cortex. Autoradiographic data also showed an increased number of dopamine receptors in kidney at 28 days after abdominal aortic constriction. These results suggest that the dopamine receptor is increased very early in heart in response to pressure overload as a result of a compensatory response to maintain an optimal left ventricular output. Kidney dopamine receptors are triggered at a later stage possibly to maintain fluid homeostasis secondary to the cardiac hypertrophic process.

Cardiac O-GlcNAc signaling is increased in hypertrophy and heart failure

2012 ◽  
Vol 44 (2) ◽  
pp. 162-172 ◽  
Author(s):  
Ida G. Lunde ◽  
Jan Magnus Aronsen ◽  
Heidi Kvaløy ◽  
Eirik Qvigstad ◽  
Ivar Sjaastad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Intracellular Signaling ◽  
Cardiac Contractility ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Novel Concept

Reversible protein O-GlcNAc modification has emerged as an essential intracellular signaling system in several tissues, including cardiovascular pathophysiology related to diabetes and acute ischemic stress. We tested the hypothesis that cardiac O-GlcNAc signaling is altered in chronic cardiac hypertrophy and failure of different etiologies. Global protein O-GlcNAcylation and the main enzymes regulating O-GlcNAc, O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and glutamine-fructose-6-phosphate amidotransferase (GFAT) were measured by immunoblot and/or real-time RT-PCR analyses of left ventricular tissue from aortic stenosis (AS) patients and rat models of hypertension, myocardial infarction (MI), and aortic banding (AB), with and without failure. We show here that global O-GlcNAcylation was increased by 65% in AS patients, by 47% in hypertensive rats, by 81 and 58% post-AB, and 37 and 60% post-MI in hypertrophic and failing hearts, respectively ( P < 0.05). Noticeably, protein O-GlcNAcylation patterns varied in hypertrophic vs. failing hearts, and the most extensive O-GlcNAcylation was observed on proteins of 20–100 kDa in size. OGT, OGA, and GFAT2 protein and/or mRNA levels were increased by pressure overload, while neither was regulated by myocardial infarction. Pharmacological inhibition of OGA decreased cardiac contractility in post-MI failing hearts, demonstrating a possible role of O-GlcNAcylation in development of chronic cardiac dysfunction. Our data support the novel concept that O-GlcNAc signaling is altered in various etiologies of cardiac hypertrophy and failure, including human aortic stenosis. This not only provides an exciting basis for discovery of new mechanisms underlying pathological cardiac remodeling but also implies protein O-GlcNAcylation as a possible new therapeutic target in heart failure.

scholarly journals Telomere dynamics during aging in polygenic left ventricular hypertrophy

2016 ◽  
Vol 48 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Francine Z. Marques ◽  
Scott A. Booth ◽  
Priscilla R. Prestes ◽  
Claire L. Curl ◽  
Lea M. D. Delbridge ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Hypertrophy ◽  
Cardiac Hypertrophy ◽  
Telomere Length ◽  
Ventricular Hypertrophy ◽  
Telomerase Activity ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Control Strain ◽  
Increased Risk

Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR) and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2 days), leading to left ventricular hypertrophy (LVH) (13 wk) and subsequently progression to heart failure (38 wk). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase ( Tert) and telomerase RNA component ( Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared with the control strain at 2 days and 38 wk, but shorter at 13 wk. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13 or 38 wk. Tert mRNA and Terc RNA were overexpressed at 38 wk, while miR-34a was overexpressed at 13 wk but downregulated at 38 wk. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer fetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13 wk, they were not present at the progression to heart failure at 38 wk.

scholarly journals Cardiac Natriuretic Peptide Profiles in Chronic Hypertension by Single or Sequentially Combined Renovascular and DOCA-Salt Treatments

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina S. Cerrudo ◽  
Susana Cavallero ◽  
Martín Rodríguez Fermepín ◽  
Germán E. González ◽  
Martín Donato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricular Hypertrophy ◽  
Cardiac Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular ◽  
Prolonged Treatment ◽  
Chronic Hypertension ◽  
Peptide Profiles

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.

Abstract 88: Cardiac-specific Deletion of Protein Tyrosine Phosphatase 1B Exacerbates Pressure Overload-induced Hypertrophy and Heart Failure in Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Gerald Coulis ◽  
Alexandre Bergeron ◽  
Yanfen Shi ◽  
David Labbe ◽  
Michel Tremblay ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Tyrosine Phosphatase ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Compensatory Hypertrophy ◽  
Mrna Levels ◽  
Compensatory Response ◽  
Left Ventricular Dilation

Cardiac hypertrophy involves the re-expression of a foetal gene program that occurs when cardiomyocytes are continuously exposed to stresses. The enlargement initially improves cardiac function, however, this compensatory hypertrophy predisposes individuals to arrhythmias, pathological hypertrophy and heart failure. Given the importance of reactive oxygen species (ROS) in the transition from cardiac hypertrophy to heart failure and the documented inhibition of PTPs by ROS, we hypothesized and explored whether specific PTPs could act as checkpoints in this process. We have identified PTP1B as a target of ROS in hearts undergoing hypertrophy. To better understand the role of PTP1B inhibition in cardiac hypertrophy, we generated cardiomyocyte-specific PTP1B knockout (PTP1B cKO) mice. Subjecting PTP1B cKO mice to pressure overload (PO) caused a dramatic left ventricular dilation and several distinctive features of heart failure when compared to control mice subjected to PO for the same period. Characterization of the mRNAs expressed in the hypertrophy-associated foetal gene program revealed that although PO led to increased mRNA levels of ANF and BNP, the increased expression of β-MHC observed in control mice subjected to PO was compromised in PTP1B cKO-PO mice. Since PTP1B inactivation can lead to the inactivation of AGO2 and compromise miRNA-mediated mRNAs repression, we investigated whether PTP1B regulated AGO2 phosphorylation and association with mRNAs in this context. We observed that AGO2 phosphotyrosine-393 levels were elevated and that AGO2 was a substrate of PTP1B in myocytes and in hearts undergoing hypertrophy. We also found changes in AGO2-mRNA associations between control- and PTP1B cKO-PO hearts and identified MED13 as a regulator of β-MHC expression that was differentially regulated by AGO2 in PTP1B cKO-PO hearts. Since increased expression of β-MHC contributes to the compensatory response that initially improves cardiac function, we will propose a model in which PTP1B inhibition regulates AGO2 activity and contributes to heart failure.

Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice

1998 ◽  
Vol 275 (2) ◽  
pp. H393-H399 ◽  
Author(s):  
Nobuaki Tanaka ◽  
Tsutomu Ryoke ◽  
Minoru Hongo ◽  
Lan Mao ◽  
Howard A. Rockman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Frequency Effect ◽  
High Dose ◽  
Mrna Levels ◽  
Force Frequency ◽  
Collagen Iii ◽  
Igf I

Cardiac hypertrophic and contractile responses were studied in mice administered growth hormone (GH) and insulin-like growth factor (IGF-I) (8 mg ⋅ kg−1 ⋅ day−1), alone or in combination (IGF-I/GH), for 2 wk. Also, changes in expression of selected left ventricular (LV) genes in response to IGF-I/GH were compared with those in other forms of cardiac hypertrophy. GH or IGF-I alone at three to four times the usual dose in rats failed to produce increases in heart and LV weights and hemodynamic effects; however, IGF-I/GH was synergistic, increasing body weight and LV weights by 39 and 35%, respectively. A measure of myocardial contractility (maximal first derivative of LV pressure, catheter-tip micromanometry) was increased by 34% in the IGF/GH group, related in part to a force-frequency effect, since the heart rate increased by 21%. Other mice were treated surgically to produce pressure overload (transverse aortic constriction) or volume overload (arteriovenous fistula) for 2 wk; LV weights were then matched to those in the IGF-I/GH group, and mRNA levels of selected markers were assessed. In contrast to the increased mRNA levels of atrial natriuretic factor, α-skeletal actin, and collagen III generally observed in overloaded hearts, changes in IGF-I/GH-treated mice were not significant. Thus high-dose IGF-I/GH produce cardiac hypertrophy and a positive inotropic effect without causing significant changes in expression of fetal and other selected myocardial genes, suggesting that this hypertrophy may be of a more physiological type than that due to mechanical overload.

Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy

1997 ◽  
Vol 272 (1) ◽  
pp. H168-H175 ◽  
Author(s):  
H. Tsutsui ◽  
Y. Ishibashi ◽  
K. Imanaka-Yoshida ◽  
S. Yamamoto ◽  
T. Yoshida ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Protein Level ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Regulatory Proteins ◽  
Control Value ◽  
Abdominal Aortic ◽  
Hypertrophied Myocardium

The alterations of intracellular calcium (Ca2+) homeostasis may be responsible for the contractile defects in pressure-overload cardiac hypertrophy. The Ca(2+)-adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR) is reduced in the hypertrophied or failing heart. However, it is not known whether Ca(2+)-storing proteins, including calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca(2+)-regulatory proteins using Western blot analysis in left ventricular (LV) muscle isolated from sham-operated control rats (n = 6) and rats with pressure overload 4 wk after abdominal aortic constriction (n = 7). The contractile function of isolated LV myocytes, assessed by the sarcomere motion measured with laser diffraction, was depressed in aortic-constricted rats. The SR Ca(2+)-ATPase protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein level was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterations in SR Ca(2+)-regulatory proteins were equally observed in hypertrophied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staining of calsequestrin in the control heart showed cross striations at the Z lines, whereas calreticulin was hardly observed within myocytes but was intense within interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed at the perinuclear region within the myocyte cytoplasm. These data indicate that pressure-overload cardiac hypertrophy causes the alterations in SR Ca(2+)-storing proteins as well as in Ca(2+)-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.

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