Age-Associated Features of the Expression Level of Apoptosis Markers in Cardiomyocytes of Patients with Dilated Cardiomyopathy

Abstract

To understand the pathogenesis of dilated cardiomyopathy (DCMP), it is necessary to establish the molecular and cellular mechanisms of myocardial aging, including those associated with programmed cell death, the molecular mechanisms of which have not been extensively studied. The aim of this work is to study markers of apoptosis in cardiomyocytes of patients with DCMP in vitro. We used the method of primary dissociated cell cultures and the method of immunofluorescence confocal laser microscopy. Cells of the 3rd and 14th passages, corresponding to “young” and “old” cultures, were used to simulate cellular senescence. At the molecular level, aging of cardiomyocyte cells was accompanied by a twofold increase in the expression of p16^INK4a compared to “young” cultures, both in the control group and in the group with DCMP. It was also found that the expression of p16^INK4a in cultures taken from patients with pathology was two times higher than in similar cultures from healthy patients. The expression of p21 was increased in the group with DCMP compared to the control; however, with aging of the culture, the expression of p21 did not change, remaining at a significant level. The most significant (3.2-fold) differences were obtained when comparing the expression of Bax in the cell culture of cardiomyocytes from the group with DCMP in the “young” culture compared with the control. Aging of myocardial cells at the molecular level was manifested in an increase in the expression of the Bax protein, which is the triggering mechanism of the mitochondrial apoptosis pathway. It is possible that this pathway of cell death is prevalent in DCMP.