Endothelial dysfunction in the pathogenesis of arterial hypertension: new diagnostic methods

Abstract

ENDOTHELIAL DYSFUNCTION IN THE PATHOGENESIS OF ARTERIAL HYPERTENSION: NEW DIAGNOSTIC METHODS Tetiana V. Talaieva State Institution «National Scientific Center «M. D. Strazhesko Institute of Cardiology, Clinical and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine», 5, Svyatoslava Khorobroho Str., Kyiv, Ukraine 03151 Introduction. Arterial hypertension (AH) remains the most widespread disease of the circulatory system, as well as one of the leading risk factors for the development of cardiovascular diseases. Recent studies indicate that endothelial dysfunction may play a key role in the pathogenesis of hypertension. Endothelial dysfunction is associated with damage and accelerated apoptosis of endothelial cells (ECs), and quite often these changes occur before morphological and clinical signs of the disease appear. The researches of the last decades established that the most important properties of the endothelium - restoration and preservation of structural and functional integrity and its reparative activity are directly related to circulating endothelial progenitor cells - precursor cells of endotheliocytes (ECCs). The use of various markers for the determination of ECCs in circulating blood, the determination of the content of exfoliated endothelial cells and the reserve function of the bone marrow (ability to produce ECCs) makes it possible to assess the function of the endothelium and the risk of the development and progression of cardiovascular diseases. Purpose: using the flow cytometry method to evaluate the possibility of determining the content of ECCs in the blood, desquamated ECs and the reserve function of the bone marrow (ability to produce ECCs) as markers of endothelial dysfunction. Materials and methods. 153 patients with AH were included in the study. All patients underwent complaint registration, history taking, general clinical examination, including office blood pressure measurement and daily blood pressure monitoring, physical examination, brachial artery compression test to assess endothelium-dependent vasodilatation. The number of ECCs of peripheral blood was determined by the method of flow cytometry with the help of reagents for the determination of differentiation clusters CD34, CD45, CD31, CD133 manufactured by "Beckman Coulter Inc.". In the conditions of the test with dosed physical load, the blood content of ECCs was determined on a bicycle ergometer before and after 60 minutes. after completing the test on 55 patients with hypertension. The results. In the studies, complex determination of various markers on the surface of the ECCs was used. At baseline, the number of ECCs (CD34+/CD45-/+) was 22 % lower in patients with hypertension, and 28 % lower in patients with resistant hypertension than in practically healthy donors (р < 0.05). The number of ECCs (CD133+ CD31+ CD45-/+) in patients with hypertension was 25 % less than in the norm. The number of desquamated cells exceeded the norm by 152 % (р < 0.001). In patients with hypertension, there was a decrease in the reserve function of the bone marrow to produce ECCs in response to ischemia caused by stress. The obtained data are confirmed by the results of the brachial artery compression test. Based on the results of the analysis in the groups with controlled and resistant hypertension, it was found that the last index of EDVD was 25 % lower than in the group of patients with hypertension that is well controlled (р < 0.05). The use of standard therapy for 12 weeks was accompanied by an increase in the number of ECCs in patients, which indicated the restoration of endothelial function after the treatment. Conclusions. In patients with hypertension, a decrease in the content of ECCs in the blood was noted. The resistant course of hypertension is associated with greater manifestations of endothelial dysfunction. Determination of ECCs using the flow cytometry method provides important additional information about endothelial dysfunction as a risk factor for the development and progression of hypertension, and can also be used to assess the effectiveness of antihypertensive therapy. Keywords: arterial hypertension, endothelium, dysfunction, endothelial progenitor cells.