This review summarizes the data available in the literature on the development, structure, and function of telocytes (TCs) and their role in the heart in health and diseases. At the present time, TCs have been found in many organs of mammals and humans. TC is a small oval cell that contains a nucleus surrounded by small amounts of cytoplasm, with extremely long and thin processes named telopodias. TCs have unique ultrastructural and immunohistochemical features; double positive labeling for CD34/PDGFR-β and CD34/vimentin is suitable for their identification. The role of TCs in the heart at different study stages is the subject of debate. There are currently available data on a decline in the number of cardiac TCs in patients with various heart diseases. Relying on a number of investigations showing that TCs are present in the subepicardial stem cell niches, the authors consider a hypothesis for the key role of cardiac TCs in the regeneration and reparation of the heart.
Background:For many decades, women in all age groups have a high risk of mortality and perioperative complications of cardiac surgery (CS), with its cause being unclear until now. Preoperative prediction of cardiovascular complications (CVC), based only on the clinical and instrumental criteria without taking gender into account, also remains unsuccessful. There is an opinion that the structural and functional changes in the myocardium, which exist before the operation, could significantly affect the patient's condition after cardiac surgery.Aim:To identify morphological and molecular predictors of unfavorable prognosis in chronic heart failure (CHF) patients of both genders after CS.Materials and methods:The study included 87 CHF patients of both genders referred for an elective cardiac surgery. Before the operation, a standard examination and treatment of CHF and concomitant disorders were performed. A sample of the right atrial appendage (RAA) myocardium that had been resected during the CS, was studied by histological, immunohistochemical (IHC) (expression of caspase-3, bcl-2, MMP-2, TIMP-1, p38α, CD-34) and morphometric methods. At days 10 to 14 after CS, the presence of CVC was assessed in all the participants. We examined the relationship between the development of CVC and morphological changes in the RAA myocardium before surgery, taking into account the patients' gender.Results:Compared to the group with the favorable postoperative course in the myocardium, in the male/female group with unfavorable post-CS course there was a significant reduction in the cardiomyocyte (CMC) diameter (13.26 ± 3.14; p < 0.01 / 13.99 ± 3.64; p < 0.01), the bulk density (BD) of CMC (55.4 ± 9.45; p < 0.01 / 51.22 ± 10.12; p < 0.01) vol. %, a trophic index (0.24 ± 0.1; p < 0.01 / 0.21 ± 0.06; p < 0.01), as well as a significant increase in the stromal BD (44.91 ± 9.23; p < 0.01 / 47.78 ± 10.12; p <0.01) vol. % and the Kernogan index (1.78 ± 0.49; p < 0.01 / 1.43 ± 0.64; p = 0.143). IHC analysis of the RAA myocardium in the male/female group with an unfavorable postoperative course showed an increase in the amount of caspase-3 (+) CMC (3.9 ± 0.46; p < 0.01 / 3.34 ± 0.4; p < 0.01), an increase in the activity of +/++/+++ p38α (3/30/69; p < 0.01 / 2/39/60; p < 0.01) %, the expression of MMP-2 (2/56/43; p < 0.01 / 0/68/31; p < 0.01) %, with a decrease in the expression of TIMP-1 (19/29/52; p < 0.01 / 8/24/67; p < 0.01) % and BD of CD-34 stromal cells (18.46 ± 8.5; p < 0.01 / 27.54 ± 5.88; p < 0.01) %, compared with groups with a favorable current.Сonclusion:The study showed the role of caspase-3, MMP-2, and CD-34 in the RAA myocardium as prognostic markers of CVC in the early postoperative period, as well as gender differences in modulation of the apoptotic pathways and inefficiency of anti-apoptotic mechanisms in the RAA myocardium. Based on the assessment of the RAA myocardial reorganization, an integral prognostic picture of the structural and functional changes in the myocardium has been proposed, which makes it possible to identify a special patient cohort with an exceptionally high risk of unfavorable course of the post-CS period.
It is known that there are features of myocardial remodeling in various heart diseases. However, the influence of signaling regulatory factors in its development and their significance in predicting a course of chronic heart failure remains unclear. The importance of key markers of apoptosis, extracellular matrix, p-38α in myocardium of patients with chronic heart failure of different etiology in the development of cardiovascular complications after cardiac surgery is considered. It has been established that the combination of heart failure with coronary heart disease, heart failure with valvular defects are specific phenotypes with a special reorganization of myocardium. With the combination of heart failure with coronary heart disease without cardiovascular complications in the myocardium, higher activity of caspase-9 and TIMP-1 was noted, and differences in morphometric data were revealed in comparison with the group of heart failure with valvular defects. In groups with an unfavorable outcome of cardiosurgical operations of different etiology of chronic heart failure, there were no differences in the morphological indices and activity of molecular markers of the myocardium. This fact allows one to consider the activation of caspase-9, MMP-9, p38α in the myocardium as prognostic markers of the unfavorable outcome of cardiac surgery in patients suffering from heart failure regardless of etiology. A higher percentage of cardiovascular complications in the combination of chronic heart failure with coronary heart disease is probably associated with a less favorable myocardial phenotype and requires a specific pharmacological correction before cardiac surgery.
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