Morphological Features of the Myocardium in db/db Mice with Genetically Determined Leptin Resistance and Glucose Metabolism Disorders after Systematic Administration of Recombinant Apolipoprotein A-I.

We studied structural reorganization of the myocardium and the indices of glucose metabolism in db/db mice of different ages and the effect of administration of recombinant apolipoprotein A-I (rApoA-I) (subcutaneously at a dose of 7 mg/kg body weight once a week) on these parameters. A 2.9-fold (p < 0.001) increase in the plasma concentration of glucose and a 6.5-fold (p < 0.001) increase in the concentration of insulin were shown in db/db mice at the age of 24 weeks in comparison with the age-matched control (C57Bl mice), which reflected glucose metabolism disorders. Administration of rApoA-I starting from the age of 8 weeks led to a 10.2% decrease in the plasma glucose concentration in mice at the age of 24 weeks, which, however, remained elevated by 2-2.6 times (p < 0.001) in comparison with the control. Administration of rApoA-I did not affect insulin levels. The main structural feature of the myocardium in db/db mice were lytic damage to cardiomyocytes with perinuclear "depletion" phenomena progressing with age (the proportion of these cardiomyocytes increased from 50% at the age of 10 weeks to 66% at the age of 24 weeks) and a decrease in the volume density of capillaries relative to the control (by 26-44%, p < 0.05) and also progressing with age. In db/db mice weekly treated with rApoA-I, degenerative and necrobiotic changes in endothelial cells and smooth muscle cells in intramural arteries were less pronounced or absent. The proportion of cardiomyocytes with lytic changes decreased in each age group after treatment with rApoA-I (by 11-22%, p < 0.05), but the pattern of myocardial remodeling did not change significantly, i.e., the volume ratios of capillaries to cardiomyocytes and connective tissue to cardiomyocytes remained reduced.