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Reduction of myocardial myoglobin in bovine dilated cardiomyopathy
J Weil1, T Eschenhagen, O Magnussen
1Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Insights
Myoglobin levels significantly decrease in heart failure, primarily due to reduced gene expression, potentially worsening energy supply issues in the heart.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Myoglobin reduction is observed in heart failure animal models, linked to energy supply issues.
- Mechanisms behind decreased myocardial myoglobin in heart failure remain unclear.
- Bovine hereditary cardiomyopathy (bCMP) models human dilated cardiomyopathy with beta-adrenoceptor desensitization.
Purpose of the Study:
- Investigate myoglobin reduction in bCMP hearts.
- Elucidate the mechanisms responsible for decreased myoglobin in this model.
Main Methods:
- Compared myoglobin protein and mRNA levels in bCMP and control hearts.
- Utilized immunohistochemistry and microscopic densitometry to assess myoglobin distribution.
- Performed slot blot analysis on ventricular and atrial RNA.
Main Results:
- Myoglobin protein decreased by 46-47% in failing ventricles compared to controls.
- Immunohistochemistry showed decreased and heterogeneous myoglobin staining in bCMP ventricular myocytes.
- Myoglobin mRNA levels were reduced by 40-50% in bCMP ventricular myocardium.
Conclusions:
- Decreased myocardial myoglobin is a common feature of end-stage heart failure.
- Reduced gene expression is the primary cause of myoglobin decrease, possibly exacerbated by myocyte leakage.
- Myoglobin reduction may contribute to the energy imbalance in heart failure.
Abstract:
Myoglobin levels are decreased in various animal models of heart failure, a change that has been associated with compromised energy supply. The underlying mechanisms by which myoglobin content decreases in failing myocardium are unknown. Bovine hereditary cardiomyopathy (bCMP) displays several characteristics of human dilated cardiomyopathy with a marked desensitization of the beta-adrenoceptor signal cascade. The aim of the present study was to investigate whether a similar reduction of myoglobin can be seen in this animal model, and to elucidate the possible mechanism of this reduction. Myoglobin protein concentration was decreased by 46-47% (P < 0.05) in left and right ventricular myocardium of failing hearts (n = 9) compared to control hearts (n = 11). No difference was found between atria of diseased and control animals. Immunohistochemistry with a polyclonal antibody against myoglobin revealed a strong and uniform labeling in cardiomyocytes of non-failing hearts. Using microscopic densitometry, immunosignals were significantly decreased in ventricular myocytes of bCMP hearts (168 +/- 5.3 v 118 +/- 8.6 arbitrary units, P < 0.05). Moreover, myoglobin was heterogeneously distributed in bCMP hearts, with single myocytes showing no staining. Slot blot analysis of total RNA demonstrated a 40-50% reduction (P < 0.05) of myoglobin mRNA levels in ventricular but not in atrial myocardium of bCMP hearts. The results support the view that a decrease of myocardial myoglobin is a general phenomenon in end-stage heart failure. It appears to be primarily due to reduced gene expression but may be aggravated by leaking from single myocytes. The decrease of myoglobin may contribute to the imbalance between energy production and energy expenditure in heart failure.