ABSTRACT
We studied the effects of apoptotic bodies of cardiomyocytes (ApBc) and fibroblasts (ApBf) on myocardial regeneration and contractility in rats and the dynamics of RNA concentrations in cardiomyocytes and fibroblasts at different stages of apoptosis. ApBc increase the contractility of rat myocardium, while ApBf reduce it. ApBc stimulate the development of clones of cardiomyocyte precursors in the myocardium, while ApBf stimulate the formation of endothelial precursor clones. In doxorubicin cardiomyopathy, ApBc, similar to the reference drug (ACE inhibitor) improve animal survival, while ApBf produce no such effect. RNA concentrations in cardiomyocytes and fibroblasts before apoptosis and at the beginning of cell death significantly differed, while in apoptotic bodies of these cells, it was practically the same. It has been hypothesized that RNA complex present in ApBc and ApBf represents an "epigenetic code" of directed differentiation of cardiac stem cells.
Subject(s)
Aging/metabolism , Cardiomyopathies/metabolism , Culture Media/pharmacology , Extracellular Vesicles/metabolism , Fibroblasts/metabolism , Myocytes, Cardiac/metabolism , Stem Cells/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Apoptosis/drug effects , Cardiomyopathies/chemically induced , Cardiomyopathies/drug therapy , Cardiomyopathies/pathology , Cell Differentiation , Clone Cells , Culture Media/chemistry , Doxorubicin/toxicity , Extracellular Vesicles/chemistry , Fibroblasts/cytology , Fibroblasts/drug effects , Fosinopril/pharmacology , Male , Myocardial Contraction/drug effects , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Primary Cell Culture , RNA/metabolism , Rats , Rats, Wistar , Signal Transduction , Stem Cells/cytology , Stem Cells/drug effectsABSTRACT
Using the cell model of regenerative cardiomyogenesis (formation of contracting cardiomyocyte colonies from resident stem cells), we found that the addition of cardiomyocyte-derived apoptotic bodies to the culture of neonatal myocardial cells stimulated proliferation and differentiation of cardiomyocyte precursors and the frequency of their contraction was 1.5-fold higher than in the control. Systemic administration of cardiomyocyte-derived apoptotic bodies to Wistar rats with chronic postinfarction heart failure during the early period of myocardial remodeling considerably improved the contractile function of the heart.