Reduction of myocardial myoglobin in bovine dilated cardiomyopathy.
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.
Weil
J
J
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Eschenhagen
T
T
Magnussen
O
O
Mittmann
C
C
Orthey
E
E
Scholz
H
H
Schäfer
H
H
Scholtysik
G
G
D000818:Animals; D015152:Blotting, Northern; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism*; D005260:Female; D006325:Heart Atria / Q000737:chemistry / Q000378:metabolism; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009211:Myoglobin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism
D009211:Myoglobin; D011506:Proteins; D012313:RNA