Aspects of molecular mechanisms in myocardial hypertrophy, particular morphological changes and cell bioenergetic characteristics in patients with dilated cardiomyopathy.

Aim: To present the particular morphological aspects of hypertrophied myocardium by determining protein expression profile, the role of creatine kinase in cardiac cell function and mitochondrial respiration using endomyocardial biopsy samples obtained at cardiac catheterization in patients with dilated cardiomyopathy (DCM).

Material And Methods: The study included 43 DCM patients (37 men and 6 women, mean age 34 +/- 8.6 years). Protein content in myocardial samples was determined by quantitative immunoblotting and electrophoresis, morphometric indices were evaluated with a JEM-100C electron microscope, and mitochondrial respiratory parameters were determined with a Clark electrode in an oxigrtaphic cell.

Results: The study of the expression of hypertrophic protein markers showed increases in the amount of tubulin on average by 42%,desmin by 33%, and skeletal myosin beta-isoform by 20%, and of smooth muscle proteins--alpha-smooth muscle actin and SM22 on average by 1.5 times. In all DCM patients C-reactive protein (CRP) level was on average 52% and that of myosin light-chain kinase (MLCK) 70% higher. The morphometric study showed variable characteristics of cardiomyocytes in the entire patient group, particularly bizarre and oversized nuclei, determining us to divide the patients into two groups. The electrophoresis analysis of total creatine kinase fraction revealed significant alterations in the expression of creatine kinase isoenzymes. Mitochondrial respiration rate after addition of creatine was very low.

Conclusions: We found a high content of myosin light-chain kinase and CRP in the myocardium of patients with DCM, proving their role in hypertrophy; and this can be used in the differential diagnosis of myocardial hypertrophy as a consequence of cardiomyocyte hypertrophy and a result of the fibrotic process. Energy disturbances are significantly more pronounced in patients with DCM, with a more significant cardiomyocyte hypertrophy and an obvious increase in the size of nuclei.