Modification of myosin protein and gene expression in failing hearts due to myocardial infarction by enalapril or losartan

Wang, Jingwei; Guo, Xiaobing; Dhalla, Naranjan S.

doi:10.1016/j.bbadis.2004.06.004

Cited by 40 publications

(51 citation statements)

References 27 publications

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“…Intrinsic properties, as characterized by changed levels of expression of particular contractile or regulatory protein genes, are considered to result in the alteration of the molecular and biochemical composition of myofibrils, and this remodelling appears to be associated with cardiac dysfunction. Because ventricular remodelling after MI is considered to play a major role in the progression of HF (240), we concluded that alterations in myofibrillar ATPase activity, myosin isozyme shift and myosin gene expression were associated with cardiac dysfunction due to MI in rats (241,242). All these changes that reflect myofibrillar remodelling were partially prevented by the blockade of the renin-angiotensin system, indicating that the activation of the reninangiotensin system may be involved in both myofibrillar and cardiac remodelling in this experimental model.…”

Section: Discussionmentioning

confidence: 97%

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

Macháčková¹,

Barta²,

Dhalla³

2006

Canadian Journal of Cardiology

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Section: Discussionmentioning

confidence: 97%

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

Macháčková¹,

Barta²,

Dhalla³

2006

Canadian Journal of Cardiology

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“…In order to examine if alterations in SR and MF activities in failing hearts with or without drug treatment occur at the level of gene expression for SR and MF proteins, mRNA levels were determined by isolating total RNA and using Northern blot analysis [30,[33][34][35][36]. By employing specific molecular probes, mRNA levels for SR Ca 2+ -pump, SR Ca 2+ -release channels (RyR), SR PLB, α-myosin heavy chain ( α-MHC), and β-myosin heavy chain (β-MHC) proteins were measured; 18S rRNA were used as internal standard.…”

Section: Northern Blot Analysis and Cardiac Gene Expressionmentioning

confidence: 99%

“…The beneficial effects of prazosin on cardiac dysfunction, cardiac remodeling and defects in SR Ca 2+ -uptake system may not be due to cardiac remodeling during 4 to 12 wks of inducing MI in rats [27,31,[33][34][35][36]. Furthermore, cardiac remodeling is considered to be a major mechanism for the development of cardiac dysfunction in failing hearts [23][24][25].…”

Section: Subcellular Activities and Sr Protein Contentmentioning

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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“…S and MI rats were randomly assigned to receive either vehicle or enalapril (E, 10 mg/kg BW per day) by gavage for 8 weeks, starting 48 hours after the induction of MI. 17 Final BW was 340 to 390 g (Table 1).…”

Section: Experimental Design 2: Long-term Effects Of the Lca Ligationmentioning

confidence: 99%

Enalapril Attenuates Downregulation of Angiotensin-Converting Enzyme 2 in the Late Phase of Ventricular Dysfunction in Myocardial Infarcted Rat

et al. 2006

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Abstract-The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensinconverting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfarction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II. Key Words: angiotensin-converting enzyme Ⅲ myocardial infarction Ⅲ renin-angiotensin system Ⅲ remodeling Ⅲ cardiac function T he renin-angiotensin system (RAS) is a more complex system than originally thought. A new angiotensin-converting enzyme (ACE), ACE2, has been recently identified as a homologue of ACE. 1 ACE2 is also a metalloprotease consisting of 805 amino acids with a considerable degree of homology to ACE (40% identity and 61% similarity). 2,3 ACE2 contains a single zinc-binding domain and is a carboxypeptidase, unlike somatic ACE, which contains 2 zinc-binding domains and is a dipeptidyl carboxypeptidase. 2 Both ACE2 and ACE are bound to the plasma membrane and must be cleaved to release the soluble enzyme. 2 Their cellular and tissue distributions are also different, in that ACE is expressed in the endothelium throughout the vasculature, whereas ACE2 is distributed to most tissues, including to the heart and kidney. 3 Analyses in vitro have shown that ACE2 cleaves angiotensin (Ang) I to Ang-(1-9), which is then cleaved by ACE to Ang-(1-7). However, ACE2 also cleaves Ang II to form Ang-(1-7). Because Ang-(1-7) is a potent vasodepressor peptide, its actions could counterbalance the vasopressor effect of Ang II. 4,5 ACE2 does not act on bradykinins and its activity is not inhibited by ACE inhibitors. 2 Although a significant activation of the RAS system occurs after myocardial infarction, 6 -10 ...

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Modification of myosin protein and gene expression in failing hearts due to myocardial infarction by enalapril or losartan

Cited by 40 publications

References 27 publications

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

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

Enalapril Attenuates Downregulation of Angiotensin-Converting Enzyme 2 in the Late Phase of Ventricular Dysfunction in Myocardial Infarcted Rat

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