Proliferative Potential of Cardiomyocytes in Hypertrophic Cardiomyopathy: Correlation with Myocardial Remodeling.

Proliferating Ki-67+ cardiomyocytes were detected in the interventricular septum myocardium of adult patients with hypertrophic cardiomyopathy. In the same patients, the severity of hypertrophy and the degree of cardiomyocyte differentiation were assessed by the content of myofibrils, ultrastructural morphology, and the pattern of connexin 43-containing gap junction distribution. Adult Ki-67+ cardiomyocytes containing sarcomeric α-actin (sarc α-act+) in the sarcoplasm (diameter 23.9±6.9 µ) were detected in the myocardium of patients with hypertrophic cardiomyopathy; their relative content varied from 2 to 3084 cells per 1 million cardiomyocytes. Small early differentiating Ki-67+/sarc α-act+ cardiomyocytes with a thin cytoplasm layer (diameter 5.9±1.7 µ) constituted from 3 to 2262 cells per 1 million cardiomyocytes. These cells were found in the myocardium with the most pronounced structural changes: hypertrophy of cardiomyocytes with signs of their partial dedifferentiation.

Age-Related Features of Cardiomyocyte Ploidy in Patients with Hypertrophic Obstructive Cardiomyopathy.

Endomyocardial biopsy samples of the interventricular septum from patients with hypertrophic cardiomyopathy isolated during myectomy were examined. We revealed significant variability of cardiomyocyte ploidy (from 2.9c to 13.5c) that directly correlated with myocyte size; the maximum ploidy was found in young patients. Ultrastructural signs of increased contractile and synthetic activity of cells were observed in patients with high DNA content in cardiomyocytes.

Resident stem cells in the myocardium of patients with obstructive hypertrophic cardiomyopathy.

Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofibrillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.

Resident cardiomyocyte precursor stem cells in the myocardium of infants of the first two years of life with tetralogy of Fallot.

We studied the content of resident myocardial stem cells, cardiomyocyte precursors, in myocardial biopsy specimens from the right ventricular outflow tract of patients of the first two years of life with tetralogy of Fallot. Myocardial resident stem cells were detected by the method of confocal immunohistochemistry using antibodies to c-kit and sarcomeric α-actin. The diameter of right ventricular cardiomyocytes was measured; the presence of myolysis zones was semiquantitatively evaluated. Electron microscopic analysis of right ventricular cardiomyocytes was performed. The data on the content of resident myocardial stem cells were compared with clinical and functional parameters of the patients and morphological peculiarities of the myocardium. C-kit-positive resident myocardial stem cells were detected in the right ventricle of 17.4% patients with tetralogy of Fallot. The content of resident myocardial stem cells in these patients varied from 4 to 45 (median 11) per 1 mln cardiomyocytes; this parameter was higher in patients with high content of small cardiomyocytes (diameter <10 µ) and cardiomyocytes with incomplete myofibril assembly in the right ventricular myocardium.