β-adrenergic blockade attenuates cardiac dysfunction and myofibrillar remodelling in congestive heart failure

Macháčková, J; Sanganalmath, Santosh K.; Elimban, Vijayan; Dhalla, Naranjan S.

doi:10.1111/j.1582-4934.2010.01015.x

Cited by 31 publications

(27 citation statements)

References 57 publications

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“…These alterations are accentuated by the infiltration of inflammatory cells which further degrade both the ECM and intracellular proteins resulting in injury that involves changes in the infarct zone as well as throughout the viable ventricular myocardium [12]. Intracellularly, MI increases the level of b-myosin heavy chain (MHC) protein and decreases the level of a-MHC protein content [91]. This shift in the pattern of MHC proteins has also been observed in the hypertrophied heart due to MI at the mRNA level [92][93][94].…”

Section: Proteases In Myocardial Infarction and Heart Failurementioning

confidence: 99%

Role of various proteases in cardiac remodeling and progression of heart failure

Müller

Dhalla

2011

Heart Fail Rev

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It is believed that cardiac remodeling due to geometric and structural changes is a major mechanism for the progression of heart failure in different pathologies including hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy, diabetic cardiomyopathy, and myocardial infarction. Increases in the activities of proteolytic enzymes such as matrix metalloproteinases, calpains, cathepsins, and caspases contribute to the process of cardiac remodeling. In addition to modifying the extracellular matrix, both matrix metalloproteinases and cathepsins have been shown to affect the activities of subcellular organelles in cardiomyocytes. The activation of calpains and caspases has been identified to induce subcellular remodeling in failing hearts. Proteolytic activities associated with different proteins including caspases, calpain, and the ubiquitin-proteasome system have been shown to be involved in cardiomyocyte apoptosis, which is an integral part of cardiac remodeling. This article discusses and compares how the activities of various proteases are involved in different cardiac abnormalities with respect to alterations in apoptotic pathways, cardiac remodeling, and cardiac dysfunction. An imbalance appears to occur between the activities of some proteases and their endogenous inhibitors in various types of hypertrophied and failing hearts, and this is likely to further accentuate subcellular remodeling and cardiac dysfunction. The importance of inhibiting the activities of both extracellular and intracellular proteases specific to distinct etiologies, in attenuating cardiac remodeling and apoptosis as well as biochemical changes of subcellular organelles, in heart failure has been emphasized. It is suggested that combination therapy to inhibit different proteases may prove useful for the treatment of heart failure.

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Section: Proteases In Myocardial Infarction and Heart Failurementioning

confidence: 99%

Role of various proteases in cardiac remodeling and progression of heart failure

Müller

Dhalla

2011

Heart Fail Rev

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“…Since the sympathetic nervous system is markedly activated in heart failure [26,27], the elevated levels of plasma catecholamines are known to play a critical role in the pathogenesis of cardiac dysfunction, cardiac remodelingmediated through the participation of both α-AR and β-AR in the myocardium. Although β-AR blockers have been demonstrated to attenuate myocardial changes in heart failure [27,28], no information regarding the beneficial effects of α-AR blockade on cardiac remodeling or subcellular defects in failing hearts is available in the literature. This study was therefore undertaken to investigate if the depressed cardiac function in rats with heart failure due to MI is improved and cardiac remodeling is attenuated upon treatment with prazosin, a well-known α-AR blocker.…”

Section: Introductionmentioning

confidence: 99%

Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Babick¹,

Elimban²,

Dhalla³

2012

J Clinic Experiment Cardiol

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Background: This study was undertaken to test if α-Adrenoceptor (AR) blockade with prazosin reverses cardiac remodeling and ameliorates subcellular defects in heart failure due to Myocardial Infarction (MI).Methods: Heart failure in rats was induced by MI for 12 wks and then treated with or without prazosin (10 mg/kg/ day) for 8 wks. Both control and experimental animals were assessed hemodynamically and echocardiographically for evaluating changes in heart function and cardiac remodeling, respectively. Left Ventricle (LV) was used for determining biomedical and molecular activities.Results: Cardiac dysfunction, as evident from depressed LV systolic pressure, rates of changes in pressure development and decay, cardiac output, ejection fraction and fractional shortening as well as increased LV end diastolic pressure, in 20 wks infarcted animals, was corrected partially by prazosin treatment. Different parameters of cardiac remodeling including increased LV posterior wall thickness and LV systolic diameter in failing hearts were fully or partially reversed whereas increased LV diastolic diameter was unaltered by prazosin therapy. Reversal of lung congestion and cardiac hypertrophy in MI animals by prazosin was associated with depression in the elevated levels of plasma norepinephrine, unlike epinephrine or dopamine. Depressions in Sarcoplasmic Reticular (SR) Ca 2+ -uptake activity as well as protein content for Ca 2+ -pump ATPase and phospholamban in failing hearts were reversed partially whereas depressed SR Ca 2+ -release activity and myofibrillar Ca 2+ -stimulated ATPase activity were not affected by prazosin. Alterations in mRNA levels for SR Ca 2+ -pump ATPase, SR Ca 2+ -release channels, and α-myosin heavy chain and β-myosin heavy chain in MI-induced heart failure were not influenced by prazosin treatment. Conclusions:It is suggested that the activation of α-AR system may be associated with cardiac remodeling and heart failure and the reverse cardiac remodeling by α-AR blockade may improve cardiac performance by attenuating defects in SR Ca 2+ -pump.

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“…Although the circulating levels of catecholamines, which promote the entry of Ca 2? into cardiomyocytes, are markedly elevated in the infarcted animals [77], the b-adrenoceptors, adenylyl cyclase, and related signal transduction mechanisms are impaired [80]. Thus, defects in Ca 2?…”

Section: Subcellular Defects Due To Myocardial Infarctionmentioning

confidence: 96%

“…with the troponin C in the thin filaments because remodeling of myofibrils as a consequence of changes in myosin isozymes and regulatory proteins have been shown to occur in heart failure [76][77][78][79]. Although the circulating levels of catecholamines, which promote the entry of Ca 2?…”

Section: Subcellular Defects Due To Myocardial Infarctionmentioning

confidence: 98%

Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging

et al. 2011

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Although several risk factors including hypertension, cardiac hypertrophy, coronary artery disease, and diabetes are known to result in heart failure, elderly subjects are more susceptible to myocardial infarction and more likely to develop heart failure. This article is intended to discuss that cardiac dysfunction in hearts failing due to myocardial infarction and aging is associated with cardiac remodeling and defects in the subcellular organelles such as sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils. Despite some differences in the pattern of heart failure due to myocardial infarction and aging with respect to their etiology and sequence of events, evidence has been presented to show that subcellular remodeling plays a critical role in the occurrence of intracellular Ca(2+)-overload and development of cardiac dysfunction in both types of failing heart. In particular, alterations in gene expression for SL and SR proteins induce Ca(2+)-handling abnormalities in cardiomyocytes, whereas those for myofibrillar proteins impair the interaction of Ca(2+) with myofibrils in hearts failing due to myocardial infarction and aging. In addition, different phosphorylation mechanisms, which regulate the activities of Ca(2+)-cycling proteins in SL and SR membranes as well as Ca(2+)-binding proteins in myofibrils, become defective in the failing heart. Accordingly, it is suggested that subcellular remodeling involving defects in Ca(2+)-handling and Ca(2+)-binding proteins as well as their regulatory mechanisms is intimately associated with cardiac remodeling and heart failure due to myocardial infarction and aging.

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β-adrenergic blockade attenuates cardiac dysfunction and myofibrillar remodelling in congestive heart failure

Cited by 31 publications

References 57 publications

Role of various proteases in cardiac remodeling and progression of heart failure

Role of various proteases in cardiac remodeling and progression of heart failure

Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging

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