Skeletal Muscle Sarcoplasmic Reticulum Ca
            2+
            -ATPase Gene Expression in Congestive Heart Failure

Patients with congestive heart failure (CHF) are prone to increased skeletal muscle fatigue. Elevated circulatory concentrations of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1, which may stimulate matrix metalloproteinase (MMP) activity and, thereby, contribute to skeletal muscle dysfunction, are frequently found in CHF. However, whether skeletal muscle MMP activity is altered in CHF is unknown. Hence, we have used a gelatinase assay to assess the activity of MMP and tissue inhibitors of MMP in single skeletal muscles of rats with CHF 6 wk after induction of myocardial infarction. Sham-operated (Sham) rats were used as controls. We also measured the gene expression and protein contents of MMP-2 and MMP-9 in skeletal muscles of these rats. Plasma MMP activity was nearly seven times higher ( P < 0.05) in CHF than in Sham rats. Concomitantly, the MMP activity within single slow- and fast-twitch skeletal muscles of CHF rats increased two- to fourfold compared with Sham animals, whereas tissue inhibitor of MMP activity did not differ ( P > 0.05). Preformed MMP-2 and MMP-9 were probably activated in CHF, because neither their gene expression nor protein levels were altered ( P > 0.05). Serum concentrations of TNF-α and monocyte chemoattractant protein-1 remained unchanged ( P > 0.05) between CHF and Sham rats during the 6-wk observation period. We conclude that development of CHF in rats enhances MMP activity, which in turn may distort the normal contractile function of skeletal muscle, thereby contributing to increased skeletal muscle fatigue.

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Sarcoplasmic reticulum Ca2+ ATPase gene expression to the rescue of myocardial contractility in hypothyroid associated heart failure

Cardiovascular Research ◽

10.1016/s0008-6363(99)00165-0 ◽

1999 ◽

Vol 43 (2) ◽

pp. 282-284

Author(s):

C Ventura

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Sarcoplasmic Reticulum ◽

Myocardial Contractility ◽

Atpase Gene

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Influence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarction

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y04-115 ◽

2004 ◽

Vol 82 (12) ◽

pp. 1118-1127 ◽

Cited By ~ 14

Author(s):

Bin Ren ◽

Qiming Shao ◽

Pallab K Ganguly ◽

Paramjit S Tappia ◽

Nobuakira Takeda ◽

...

Keyword(s):

Gene Expression ◽

Myocardial Infarction ◽

Heart Failure ◽

Congestive Heart Failure ◽

Sarcoplasmic Reticulum ◽

Cardiac Function ◽

Term Treatment ◽

Cardiac Performance ◽

Long Term Treatment

Although it is generally accepted that the efficacy of imidapril, an angiotensin-converting enzyme inhibitor, in congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR) proteins has not been fully understood. In this study, we examined the effects of long-term treatment of imidapril on mortality, cardiac function, and gene expression for SL Na+/K+ ATPase and Na+–Ca2+ exchanger as well as SR Ca2+ pump ATPase, Ca2+ release channel (ryanodine receptor), phospholamban, and calsequestrin in CHF due to myocardial infarction. Heart failure subsequent to myocardial infarction was induced by occluding the left coronary artery in rats, and treatment with imidapril (1 mg·kg–1·day–1) was started orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed hemody nam ically and the heart and lung were examined morphologically. Some hearts were immediately frozen at –70 °C for the isolation of RNA as well as SL and SR membranes. The mortality of imidapril-treated animals due to heart failure was 31% whereas that of the untreated heart failure group was 64%. Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced morphological changes in the heart and lung. The depressed SL Na+/K+ ATPase and increased SL Na+–Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing hearts were partially prevented by imidapril. Although changes in gene expression for SL Na+/K+ ATPase isoforms as well as Na+–Ca2+ exchanger and SR phospholamban were attenuated by treatments with imidapril, no alterations in mRNA levels for SR Ca2+ pump proteins and Ca2+ release channels were seen in the untreated or treated rats with heart failure. These results suggest that the beneficial effects of imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression.Key words: sarcolemmal Na+/K+ ATPase, Na+–Ca2+ exchange, sarcoplasmic reticulum, heart failure, ACE inhibition.

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