Роль апоптоз индуцирующего фактора и окислительного стресса при хронической сердечной недостаточности

Abstract

Метою даної роботи є вивчення маркера апоптозу і окисного стресу, а також показників ушкодження ендотелію цистатіна С і ліпідного обміну у хворих з ХСН і виявлення взаємозв’язку між цими показниками. У дослідження включені 114 хворих (чоловіків і жінок) з хронічною серцевою недостатністю (ХСН). Хворі були розділені на 3 групи: I група - 39 хворих ХСН, II група - 41 хворих ХСН і СД-2, а в III групі - 34 хворих ХСН з метаболічним синдромом. Отримані нами результати дають можливість припускати, що окислювальний стрес і апоптоз тісно взаємопов’язані і впливають на прогресування ХСН і досліджувані показники можуть служити маркерами ускладнень; Целью данной работы является изучение маркера апоптоза и окислительного стресса, а также показателей повреждения эндотелия цистатина С и липидного обмена у больных с ХСН и выявление взаимосвязи между этими показателями. В исследование включены 114 больных (мужчин и женщин) с хронической сердечной недостаточностью (ХСН). Больные были разделены на 3 группы: I группа - 39 больных ХСН, II группа - 41 больных ХСН и СД-2, а в III группе -34 больных ХСН с метаболическим синдромом. Полученные нами результаты дают возможность предполагать, что окислительный стресс и апоптоз тесно взаимосвязаны и оказывают влияние на прогрессирование ХСН и исследуемые показатели могут служить маркерами осложнений; The purpose of this work is to study the marker of apoptosis and oxidative stress, as well as indicators of endothelial damage - cystatin C and lipid metabolism in patients with congestive heart failure (CHF), and to identify the relationship between these indicators. The study included 114 patients (men and women) with CHF. Patients were divided into 3 groups: group I - 39 patients with CHF, group II - 41 patients with CHF and DM-2, and group III - 34 patients with CHF with metabolic syndrome. The control group consisted of 10 healthy donors. The research was conducted in compliance with the Declaration of Helsinki (1975) which was revised in 1989 in Hong Kong. In all patients biochemical parameters of blood plasma were determined, as well as markers of oxidative stress and cystatin C. From biochemical indicators, the concentrations of total cholesterol (TC), a-lipoprotein cholesterol, р-lipoprotein cholesterol, glycosylated hemoglobin (HbAlc), glucose and triglycerides were measured. The content of nitric oxide and thiol status was investigated as markers of oxidative stress. In addition, concentrations of apoptosis inducing factor and cystatin C were determined. Biochemical indicators of total cholesterol (TC), a-lipoprotein cholesterol, р-lipoprotein cholesterol, glycosylated hemoglobin (HbAlc), glucose and triglycerides were determined using “Human” reagent kits (Germany). Concentrations of apoptosis inducing factor and cystatin C were measured with commercial sets from “USCN Life Science Inc” (China), nitric oxide concentration - using “R&D System” kit, and thiol status - with the help of kit from “Immunidiagnostik” company. Statistical analysis was performed using the Wilcoxon non-parametric criterion (Mann-Whitney test), the differences were considered significant at p<0,05, p<0,001, p<0,01. When comparing the average values in patients with CHF and CHF with metabolic syndrome and type 2 diabetes mellitus, concentrations of cholesterol and triglycerides were found to increase in all studied groups relative to control group. At the same time, a-LP cholesterol decreased in all groups with respect to control. An increase in all groups relative to control was observed for p-LP cholesterol. The hypercholesterolemia and hyper-p-lipoproteinemia observed by us contribute to damage of the vascular endothelium due to atherogenase. It has been established that high-density lipoproteins, the main anti-atherogenic fraction of lipoproteins, protect endothelial cells from apoptosis, thereby providing an important and new aspect of their anti-atherogenic activity. Caspase-independent AIF-mediated pathway plays a critical role in the hypertrophy of cardiomyocytes. A high concentration of glucose increases the apoptosis activity of caspase 3 and promotes the release of the apoptosis factor (AIF). In our studies, the AIF level increased in all groups compared with the control group. The disturbance of NO metabolism plays a major role in endothelial dysfunction, which is an integral part of the pathogenetic mechanism of CHF. The nitric oxide increased in all studied groups relative to control. Excessive amounts of NO initially perform a compensatory function aimed at improving tissue perfusion. Further it leads to activation of oxidative stress, apoptosis and increased myocardial dysfunction. The revealed violations of thiol status also reflect the degree of oxidative stress in patients with CHF. In all studied groups, there was a decrease in this indicator compared to the control group. The decrease in the level of thiol status was due to the presence and severity of CHF. This result indicates that a decrease in thiols can be an important factor in the development of CHF, since they are capable of blocking apoptosis. To characterize the complications of CHF, the level of cystatin C was examined. An increase in this indicator was revealed in all studied groups, compared to control. Elevated levels of cystatin C, independently of other factors, are associated with the severity of induced ischemia. Normally, cystatin C, an inhibitor of cysteine proteinases, prevents the development of atherosclerotic lesions. Cystatin C in patients with diabetes mellitus-2 can serve as a reliable predictor of the development of cardiovascular complications. Our data allow to assume that oxidative stress and apoptosis are closely interrelated and influence the progression of CHF and that the studied indicators can serve as markers of complications.