Background and Objectives: Coronary artery disease (CAD) is the foremost cause of adult disability and mortality. There is an urgent need to focus on the research of new approaches for the prevention and treatment of CAD. Materials and Methods: The effects of peptides isolated from the blood plasma of CAD patients on endothelial cell secretion using the in vitro model have been tested. Human endothelial progenitor cells (HEPCs) were incubated for 24 h with peptides isolated from the plasma of healthy subjects or patients with stable angina, progressive unstable angina, and myocardial infarction. The contents of some soluble anticoagulant as well as procoagulant mediators in HEPC culture treated with peptide pools were then compared. Results and Conclusion: The results show that peptides from the plasma of patients with myocardial infarction promote endothelial cells to release both von Willebrand factor and endothelin-1, increasing vasoconstriction and shifting hemostatic balance toward a prothrombotic state. In contrast, peptides from the plasma of patients with progressive unstable angina suppress the secretion of endothelin-1 by HEPCs, while the secretion of both von Willebrand factor and tissue plasminogen activator was increased. As can be seen from the results obtained, disease derived peptides may contribute to the homeostasis of living organisms or the progression of pathological processes.
Coronary artery disease (CAD) is a major public health problem all over the world, and although diagnostic and treatment approaches are improving, the majority of individuals who suffer CAD will not survive. Therefore, it is a clinical demand to find out new biomarkers for identification of CAD in the earlier stage. The purpose of this study was to determine whether qualitative and quantitative alterations of plasma soluble fibrin monomer complexes (SFMCs) are associated with cardiovascular events. Additionally, some other well-known biomarkers of hypercoagulation state, such as fibrinogen, and prothrombin were analyzed in plasma of patients with different coronary artery pathologies. We found that plasma SFMC concentrations were remarkably increased in all tested CAD groups. Moreover, the development of CAD was accompanied by the changes in both quantity and quality of SFMC composition compared to that of healthy subjects. Our results also demonstrated the elevated level of high molecular weight vitamin K-dependent protein (VKDP) complexes in plasma of CAD patients which could be used as a potential biomarker of hypercoagulation state. More studies are clearly needed to investigate whether SFMCs or abnormal forms of VKDPs affect cardiovascular events under CAD development and progression.
The hemostasis system is a functional system of the human body that ensures the integrity and patency of the vessels of the circulatory system, prevents or stops bleeding, and also maintains the blood in a liquid state. The functioning of the hemostasis system is based on a balanced interaction between its coagulation, anticoagulation and fibrinolytic links. According to modern concepts, destabilization of hemovascular homeostasis is one of the main mechanisms of progression of coronary heart disease (CHD). Biologically active substances of endogenous origin can play the role of triggers of cardiovascular events, along with generally accepted factors such as obesity, arterial hypertension, diabetes and smoking. Establishing the nature of genesis factors and mechanisms of progression of cardiovascular symptoms will increase the probability of a positive prognosis for patients with coronary heart disease, which remains the most common cause of mortality in the population of developed countries. The purpose of this study was to find out the level of some biologically active substances, including certain factors of the coagulation cascade and the fibrinolysis system, parameters of tryptophan metabolism and heat shock proteins (namely, HPS 60 and HPS 70), in patients with coronary artery disease. 66 patients diagnosed with coronary artery disease took part in the study: 20 of them had a confirmed diagnosis of stable angina, 28 had progressive unstable angina, and 18 had myocardial infarction. The results of the study showed an increased production of prothrombotic mediators (Willebrand factor, serotonin) in the blood plasma of patients with coronary artery disease. An imbalance between tissue plasminogen activator and its inhibitor was also noted, which may be the main factor in reducing the fibrinolytic potential of blood plasma under cardiovascular events. It has been established that patients with coronary heart disease, regardless of the form of the disease, are characterized by a significant increase in the plasma content of heat shock protein, namely HPS 60. Such results suggest the possible involvement of this protein in the pathological reactions that occur during coronary heart disease, and the possibility of its use as a biomarker of cardiovascular diseases.
Coronary heart disease is the most common form of cardiovascular disease, which is one of the leading causes of death and disability worldwide. Today, the search for effector molecules of endogenous origin and investigation of their possible role as new therapeutic targets and biological markers are underway. Among such molecules, special attention should be paid to immunoglobulins G (IgG), which accumulate in the general bloodstream in response to the appearance in the body of atypical and modified proteins, as well as their fragments, which is a natural consequence of activation of inflammatory and hypercoagulation reactions under coronary heart disease. In this study, in experimentsin vitro, we investigated the effect of IgG obtained from the serum of patients with unstable angina and myocardial infarction on platelet aggregation and endothelin-1 and von Willebrand factor secretion by cells in HUVEC culture. We did not observe any effect of IgG obtained from the serum of patients with coronary heart disease, both on platelet activation and on the dynamics of ADP-dependent cell aggregation. However, the addition of IgG to the HUVEC cell culture medium showed an increase in cell secretion of both von Willebrand factor and endothelin-1. High concentrations of von Willebrand factor in the systemic circulation can cause an increase in prothrombotic potential, while the accumulation of endothelin-1 may contribute to the development of hypoxia in both the myocardium and other peripheral tissues. All this can lead to disruption of coagulation processes, and, as a consequence, the development and progression of complications of coronary heart disease. It should be noted that antibodies obtained from the serum of patients with progressive unstable angina had the most pronounced effect. The obtained results reveal new perspectives in the study of the effector properties of antibodies and their role in the pathogenesis of coronary heart disease.
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