One of the main forms of cardiovascular diseases is coronary heart disease (CHD) but degenerative aortic valve (AoV) stenosis is the most frequent native valve disease. Both CHD and degenerative AoV stenosis have common risk factors such as age, high blood cholesterol, diabetes, smoking, high blood pressure, inflammation, and metabolic syndrome. Not only risk factors, but also pathophysiological changes, especially in the early stages of degenerative aortic valve stenosis, are similar to atherosclerosis - endothelial damage, lipid deposition, focal sclerosis, inflammatory cell infiltration, cytokine release and calcification. However, these conditions are not always observed at the same time. This confirms the existence of risk and pathogenesis factors specific to each disease. Although these heart diseases have been known for a long time and are intensively studied, there is still a lack of reliable markers that could help predict disease progression, the need for further surgery and mortality, therefore the pathophysiological processes involved in disease pathogenesis should be re-evaluated. Tissue changes in these diseases are complex and include cell death, cardiac innervation, tissue ischemia, regulators of metabolism and homeostasis, markers of inflammation and anti-inflammation, and other changes that are still not fully understood. Aim of the study: to determine the prevalence of markers of apoptosis, homeostasis regulating factors, innervation, ischemia and inflammation in right atrial tissue in cases of coronary heart disease and degenerative aortic valve stenosis. The tissue material used in the study – fragments of the right atrial appendage collected during elective open heart surgeries. A total of 36 patients with acquired heart diseases were included in the study – 24 patients with coronary heart disease and 12 patients with degenerative aortic valve stenosis. Samples of right atrial tissue from 5 patients with congenital heart disease operated at an early age were used as the study control group. Tissues were stained with hematoxylin and eosin for routine light microscopy, treated with the biotin-streptovidine method for immunohistochemical detection of tissue markers and by the TUNEL method for the detection of apoptotic cells. The following markers were identified in right atrial tissue by immunohistochemistry: atrial natriuretic peptide (ANUP), PGP 9.5- containing innervation, vascular endothelial growth factor (VEGF), chromogranin A (ChgA), endothelin 1 (ET-1), interleukin 1α (Il-1α ), interleukin 10 (II-10), β defensins 2, 3 and 4 (βD2, βD3 and βD4, respectively). Right atrial tissue in both CHD and degenerative AoV stenosis is characterized by non-specific degenerative morphological changes – pronounced vacuolization as well as changes in the shape and size of cardiomyocytes and their nuclei. In addition, these patients have a high proportion of apoptotic cardiomyocytes. Although there were no significant lesions in the coronary arteries in patients with AoV stenosis, connective tissue ingrowth and vascular sclerosis were observed in some patients in both groups. In the case of CHD and degenerative AoV stenosis, activation of the right atrial endocardial endothelial cells occurs, characterized by a change of shape from flat to cubic and rich release of ChgA, ET-1, Il-1α, Il-10, βD2 and βD3. Patients with CHD and AoV stenosis in the right atrial tissue had statistically significant higher numbers of ANUP-positive cardiomyocytes, all types of IL-10 positive cells and βD2 and βD3-positive endocardial endothelial cells, but fewer ChgA-positive cells than controls or patients with congenital heart disease. Thus, in both cases of acquired heart disease, an anti-inflammatory response prevails in the right atrial tissue, but increased activity of the neuroendocrine system is more common in patients with congenital heart disease at an early age. Although some tendencies were observed, for example, in the CHD group, there were slightly more VEGF, ET-1, Il-1α positive endocardial endothelial cells, Il-10 positive cardiomyocytes, connective tissue and endothelial cells, but in AoV stenosis group, there were slightly more ChgA-positive endocardial endothelial cells, however, these differences did not reach statistical significance. The most striking finding in our study was the rich expression of antimicrobial peptides, such as human β defensins 2 and 3, in the right atrial tissues in patients with CHD, degenerative AoV stenosis and congenital heart disease.
Right Atrial Morphology in Coronary Heart Disease and Degenerative Aortic Valve Stenosis. Summary of the Doctoral Thesis
