Characterization of cardiac hypertrophy and heart  failure due to volume overload in the rat

Alterations in general characteristics and morphology of the heart, as well as changes in hemodynamics, myosin heavy chain isoforms, and β-adrenoceptor responsiveness, were determined in Sprague-Dawley rats at 1, 2, 4, 8, and 16 wk after aortocaval fistula (shunt) was induced by the needle technique. Three stages of cardiac hypertrophy due to volume overload were recognized during the 16-wk period. Developing hypertrophy occurred within the first 2 wk after aortocaval shunt was induced and was characterized by a rapid increase of cardiac mass in both left and right ventricles. Compensated hypertrophy occurred between 2 and 8 wk after aortocaval shunt where normal or mild depression in hemodynamic function was observed. Decompensated hypertrophy or heart failure occurred between 8 and 16 wk after aortocaval shunt and was characterized by circulatory congestion, decreased in vivo and in vitro cardiac function, and a shift in myosin heavy chain isozyme expression. However, the positive inotropic effect of isoproterenol was augmented at all times during the 16-wk period. Characterization of β-adrenoceptor binding in failing hearts at 16 wk revealed a significant increase in β1-receptor density, whereas β2-receptor density was unchanged. Consistent with this, basal adenylyl cyclase activity was significantly increased, and both isoproterenol- and forskolin-stimulated adenylyl cyclase activities were also increased. These results indicate that upregulation of β-adrenoceptor signal transduction is a unique feature of cardiac hypertrophy and failure induced by volume overload.

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Overt expression of AP-1 reduces alpha myosin heavy chain expression and contributes to heart failure from chronic volume overload

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2007.07.046 ◽

2007 ◽

Vol 43 (4) ◽

pp. 465-478 ◽

Cited By ~ 19

Author(s):

Grace Freire ◽

Catherina Ocampo ◽

Nadim Ilbawi ◽

Andrew J. Griffin ◽

Madhu Gupta

Keyword(s):

Heart Failure ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Volume Overload ◽

Chronic Volume Overload

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The baboon model for pressure-induced cardiac hypertrophy: Characterization of myosin isozymes and myosin heavy chain gene expression in baboon hearts

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(87)80716-2 ◽

1987 ◽

Vol 19 ◽

pp. S31-S31

Author(s):

J HIXSON ◽

J VANDEBERG ◽

R WALSH

Keyword(s):

Gene Expression ◽

Cardiac Hypertrophy ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Chain Gene ◽

Heavy Chain Gene ◽

Myosin Heavy Chain Gene ◽

Myosin Isozymes ◽

Baboon Model

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Myosin heavy chain expression and atrophy in rat skeletal muscle during transition from cardiac hypertrophy to heart failure

International Journal of Experimental Pathology ◽

10.1046/j.1365-2613.2003.00351.x ◽

2003 ◽

Vol 84 (4) ◽

pp. 201-206 ◽

Cited By ~ 26

Author(s):

Robson Francisco Carvalho ◽

Antonio Carlos Cicogna ◽

Gerson Eduardo Rocha Campos ◽

Jeane Marlene FogaÇa De Assis ◽

Carlos Roberto Padovani ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Cardiac Hypertrophy ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Rat Skeletal Muscle

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Expression of protein kinase C isoforms in cardiac hypertrophy and heart failure due to volume overload

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y05-120 ◽

2006 ◽

Vol 84 (2) ◽

pp. 227-238 ◽

Cited By ~ 17

Author(s):

Emmanuelle Sentex ◽

Xi Wang ◽

Xueliang Liu ◽

Anton Lukas ◽

Naranjan S. Dhalla

Keyword(s):

Heart Failure ◽

Protein Kinase C ◽

Protein Kinase ◽

Cardiac Hypertrophy ◽

Volume Overload ◽

Aortocaval Shunt ◽

Kinase C ◽

Pkc Β ◽

Pkc Ζ ◽

Protein Kinase C Isoforms

The present study determined whether changes in the activity and isoforms of protein kinase C (PKC) are associated with cardiac hypertrophy and heart failure owing to volume overload induced by aortocaval shunt (AVS) in rats. A significant increase in Ca2+-dependent and Ca2+-independent PKC activities in the homogenate and particulate fractions, unlike the cystolic fraction, of the hypertrophied left ventricle (LV) were evident at 2 and 4 weeks after inducing the AVS. This increase coincided with increases in PKC-α and PKC-ζ contents at 2 week and increases in PKC-α, PKC-β1, PKC-β2, and PKC-ζ contents at 4 weeks in the hypertrophied LV. By 8 and 16 weeks of AVS, PKC activity and content were unchanged in the failing LV. On the other hand, no increase in the PKC activity or isoform content in the hypertrophied right ventricle (RV) was observed during the 16 weeks of AVS. The content of Gαq was increased in the LV at 2 weeks but then decreased at 16 weeks, whereas Gαq content was increased in RV at 2 and 4 weeks. Our data suggest that an increase in PKC isoform content neither plays an important role during the development of cardiac hypertrophy nor participates in the phase leading to heart failure owing to volume overload.

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Effects of Trandolapril on Structural, Contractile and Electrophysiological Remodeling in Experimental Volume Overload Heart Failure

Frontiers in Pharmacology ◽

10.3389/fphar.2021.729568 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dagmar Jarkovská ◽

Matúš Miklovič ◽

Jitka Švíglerová ◽

Luděk Červenka ◽

Petra Škaroupková ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Hypertrophy ◽

Cardiac Remodeling ◽

Volume Overload ◽

Ace Inhibition ◽

Therapeutic Effects ◽

Aortocaval Shunt ◽

Needle Technique ◽

Chronic Volume Overload ◽

Eccentric Hypertrophy

Chronic volume overload induces multiple cardiac remodeling processes that finally result in eccentric cardiac hypertrophy and heart failure. We have hypothesized that chronic angiotensin-converting enzyme (ACE) inhibition by trandolapril might affect various remodeling processes differentially, thus allowing their dissociation. Cardiac remodeling due to chronic volume overload and the effects of trandolapril were investigated in rats with an aortocaval fistula (ACF rats). The aortocaval shunt was created using a needle technique and progression of cardiac remodeling to heart failure was followed for 24 weeks. In ACF rats, pronounced eccentric cardiac hypertrophy and contractile and proarrhythmic electrical remodeling were associated with increased mortality. Trandolapril substantially reduced the electrical proarrhythmic remodeling and mortality, whereas the effect on cardiac hypertrophy was less pronounced and significant eccentric hypertrophy was preserved. Effective suppression of electrical proarrhythmic remodeling and mortality but not hypertrophy indicates that the beneficial therapeutic effects of ACE inhibitor trandolapril in volume overload heart failure might be dissociated from pure antihypertrophic effects.

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Alterations of adenylyl cyclase and G proteins in aortocaval shunt-induced heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00798.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. H118-H125 ◽

Cited By ~ 10

Author(s):

Xi Wang ◽

Emmanuelle Sentex ◽

Donald Chapman ◽

Naranjan S. Dhalla

Keyword(s):

Heart Failure ◽

Protein Content ◽

Adenylyl Cyclase ◽

G Proteins ◽

Mrna Level ◽

Volume Overload ◽

Experimental Models ◽

Mrna Levels ◽

Aortocaval Shunt ◽

Failing Heart

Unlike most other experimental models of congestive heart failure, the volume overload model induced by aortocaval shunt (AVS) in rats was found to exhibit enhanced β-adrenoceptor (β-AR) signaling. To study whether the adenylyl cyclase (AC)-G protein system is involved in such a change, we examined cardiac AC activity and protein content as well as Gsα and Giα activities, protein contents, and mRNA levels in both left (LV) and right (RV) ventricles at the failing stage (16 wk after surgery). Basal and forskolin-stimulated AC activities were significantly increased in both LV and RV from the failing hearts; this change was associated with an upregulation of type V/VI AC protein. In contrast to 5′-guanylyl imidodiphosphate and NaF, the stimulatory effect of isoproterenol on AC was increased in the failing heart. Although Gsα and Giα protein contents in the failing hearts were not altered, the mRNA level for Gsα was decreased by 20% and that for Giα was increased by 20%. In addition, the activity of Gsα, but not Giα, as assessed by toxin-catalyzed ADP ribosylation, was significantly decreased in the failing heart. Losartan and imidapril treatments improved cardiac function and attenuated alterations in mRNA levels for Gsα and Giα proteins, as well as Gsα activity, without affecting changes in AC protein content or activities in heart failure due to volume overload. These data suggest that increased AC activity may contribute to the enhanced β-AR signaling in the AVS model of heart failure, whereas alterations in gene expression for G proteins may be of an adaptive nature at this stage of heart failure.

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The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

Molecular and Cellular Biology ◽

10.1128/mcb.24.19.8705-8715.2004 ◽

2004 ◽

Vol 24 (19) ◽

pp. 8705-8715 ◽

Cited By ~ 31

Author(s):

Carmen C. Sucharov ◽

Steve M. Helmke ◽

Stephen J. Langer ◽

M. Benjamin Perryman ◽

Michael Bristow ◽

...

Keyword(s):

Heart Failure ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Human Heart ◽

Ventricular Myocytes ◽

Major Effect ◽

Neonatal Rat ◽

Chain Gene ◽

Human Heart Failure ◽

Peptide Mass

ABSTRACT Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure.

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