The morphology and markers of the immobilizing interstitial fibrosis of the heart

The fibrosis is the most important component of restoring the integrity of tissues and organs after their damage. In the heart, this is a fundamental stage in the process of its remodeling and, at the same time, the central link in the development and progression of chronic circulatory insufficiency. It is known that the main cause of heart failure is cardiomyocyte dysfunction, primarily as a result of coronary heart disease. However, patients often occur without obvious signs of myocardial damage proper. Our long-term clinical practice, numerous scientific and experimental studies allowed us to suggest that the cause of this phenomenon is a mechanical factor located outside the myocardial bundles of healthy cardiomyocytes, but structurally closely related to them-the interstitial connective tissue with altered physical properties. This phenomenon is called the immobilizing interstitial fibrosis of the heart. Objective: to study the morphology of connective tissue and the expression of various fibrogenic markers in immobilizing interstitial fibrosis of the heart. Materials and methods. The study was performed on the basis of the pathoanatomical department of the N.I. Pirogov NMHC. Group I (n = 30) - patients with immobilizing interstitial fibrosis of the heart, whose cause of death was heart failure. II (n = 10) is a comparison group (without diseases of the cardiovascular system). Age of patients: 68±6.5 years (group I), 29±5.1 years (group II). Heart weight: 486±141 g (group I), 322±32 g (group II). Histological sections were stained with hematoxylin and eosin, according to Van Gieson, Weigert and Masson (trichrome method). An immunohistochemical analysis was performed. Results. Statistical differences in the area of the common fibrosis zone were revealed between the groups: 13.7±7.4% (group I), 5.6±4.2% (group II), p = 0.001; MMP-9 expression: 14691±5256 in 1 mm2 (group I), 7116±2831 in 1 mm2 (group II), p = 0.0001. Tenascin-C was determined in patients with the initial stage of the interstitial fibrosis. In the comparison group, the expression of tenascin-C and Bcl-2 was not detected. The studied groups differed in the amount of detected connexin-43: 24724±14764 in 1 mm2 (group I), 38228±13548 in 1 mm2 (group II), p = 0.02; fibronectin: 3354±719 in 1 mm2 (group i), 1635±557 in 1 mm2 (group II), (p = 0.00003). Significant differences between the groups in the volume of collagen fibers of type I were revealed: 4673±1292 in 1 mm2 (group I), 2269±887 in 1 mm2 (group II), p = 0.0001; type III: 6959±1385 in 1 mm2 (group I), 2566±568 in 1 mm2 (II group), p = 0.00001. Conclusion. Deciphering the molecular and structural foundations of myocardial rearrangement in fibrosis is the key to understanding the pathogenetic foundations of the development of heart failure. The immobilizing interstitial fibrosis of the heart is based on the process of changing the connective tissue framework, leading to an increase in its density, limiting the function of cardiomyocytes. Immunohistochemi-cal examination and determination of markers of fibrous rearrangement of the heart can improve the diagnosis at the early stages of the development of the disease and prevent its progression.