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.