Homeostasis Regulating Factors, Innervation, Ischemia and Inflammatory Markers in the Right Atrial Tissue from Patients with Degenerative Aortic Valve Stenosis and Coronary Heart Disease

Abstract

Both coronary heart disease (CHD) and degenerative aortic valve (AoV) stenosis have common risk factors, such as age, high blood cholesterol, diabetes, smoking, high blood pressure, inflammation, and metabolic syndrome. However, these diseases are not always observed together, confirming the existence of risk and pathogenesis factors specific to each disease. The aim of this study was to identify presence and distribution of common and different homeostasis regulating factors, innervation, ischemia and inflammatory markers in the right atrial tissue from patients with degenerative AoV stenosis and CHD. During elective cardiac surgery, right atrial tissue fragments were taken from 20 patients with CHD and from 9 patients with degenerative AoV stenosis. All tissue fragments were stained for immunohistochemical detection of protein-gene peptide 9.5 (PGP 9.5), atrial natriuretic peptide (ANUP), vascular endothelial growth factor (VEGF), chromogranin A, endothelin, interleukin 1 and 10 (Il-1 and Il-10) and defensins 2, and 3 (D2 and D3). For the quantification of structures, a semi-quantitative counting method was used. Mostly numerous Il-10 positive cardiomyocytes and epi-/endocardial endothelial cells were detected in all specimens taken from patients with CHD, and statistically more than in specimens taken from patients with degenerative AoV disease (p = 0.007 and p = 0.016). Also, the number of D3 positive cardiomyocytes was higher in the coronary heart disease group (p = 0.026). All other tested markers such as PGP 9.5, ANUP, VEGF, endothelin, chromogranin A, Il-1 and D2 showed similar expression in both groups. Increased production of ANUP in right atrial tissue characterises both CHD and degenerative AoV stenosis. Production of ChgA in right atrial endocardial endothelial cells might represent regulation of sympathetic activity as a compensatory homeostatic response. Increased PGP 9.5-containing innervation is characteristic in patients with degenerative AoV disease and secondary mitral insufficiency. A stable increase of VEGF and variations of endothelin without statistically significant difference suggest influence of ischemia on the local vascular blood supply. Decreased production of Il-1 together with moderate to rich production of Il-10, D2, and D3 indicates the dominance of the local immune system over inflammation.