UDK: 616. 987.5 – 065

S.R.Melenko, V.D.Sorokhan

Bukovinian State Medical University, Chernivtsi, Ukraine

Von Willebrand factor as a marker of endothelium disfunction on patints with HIV/AIDS

Resume. HIV/AIDS is a global problem. Patients with HIV have endothelium disfunction. It is characterized by high concentration of bioactive substances in the blood plasma. One of these substances is a von Willebrand factor (vWF). The concentration of this substance varies during the different stages of disease.

Key words: HIV, von Willebrand factor, endothelium disfunction.

HIV/AIDS morbidity is high worldwide. The developing countries have higher morbidity [2]. There is a steady increase of HIV/AIDS morbidity in all postsoviet unian republics beginning from 90th of last century [1].The researchers started paying attention to the endothelium function in pathogeny of HIV lately. It is known that endothelium form internal layer of vessels, forming a physiologic barrier between tissues and blood. The endothelium system is considered as independent active organ that provides the homoeostasis of vascular wall [9, 10].

Endothelium has different phenotype both in the vessels of different organs and within the limits of each organ [4]. At the same time functional heterogeneity of endothelium is not fixed, but depends on signals from surrounding tissues [7]. Endothelium is morphologically and functionally adjusted to operate to the necessities of tissues, which it covers. In reply to the signals of environment, especially cytokines, there are deep changes in expressions of genes and functions in the endothelium, due to which the endothelium participates actively in the processes of inflammation, immune and homoeostatic reactions [8].

Consequently, the endothelium barrier is the dynamic, variable system, which natively reacts on various irritants both from the side of blood and from the side of nearby cells and tissues and, thus, participates actively in the physiopathology changes of this area of the vascular system [6].

A wide spectrum of bioactive substances is produced by the endothelium. Some bioactive substances are accumulated and released into bloodstream during activating or damaging of the endothelium (von Willebrand factor, E-selectin, tissue plasminogen activator) [4].

Presently, the definition of endothelium disfunction (ED) is the state of activation and damage of endothelium as correlated processes. Activation is a physiology reaction, however it can lead to ED with the damage of cells. The result of both processes could be an apoptosis of endothelium [5].

ED was traditionally used at description of physiopathology mechanisms of development of atherosclerosis and other diseases of the cardiovascular system in world literature [12, 13]. Nowadays, the list of diseases with well-proven endothelium damage was broadened. It includes both non-infectious and infectious diseases (cytomegalovirus infection, HIV, Ebola and Marburg fevers, leptospirosis) [11].

ED can be a result of the action of multiple pathologic factors and characterized by increased production of bioactive substances by endothelium [10].

A research purpose is the study of content of von Willebrand factor in blood plasma of patients with HIV/AIDS, its changes depending on the clinical stage, features of illness course and correlation with the indexes of the state of cellular link of immunity system.

Materials and methods

60 patients with HIV aged from 19 to 44 years were examined (30 men and 30 women). 23 persons (38,3%) were in the I clinical stage of HIV, 3 (5%) – in II, 25 (41,7%) – in III and 9 (15%) – in the IV stage (terminal). Patients with I and II clinical stage of HIV were incorporated in the first study group, and patients with III and IV – in the second study group accordingly. Patients did not receive antiretroviral treatment.

The control group was made by 20 healthy persons of both sexes and the same age.

For determination von Willebrand factor, blood was drawn on the morning before meal in test tubes with 3,8% citrate sodium, centrifugated at 3000 rpm. During 10 min for the separation of plasma, the got samples were stored at a temperature –20ºC before the conduction of analysis. Von Willebrand factor was tested by an immunoassay method with the use of test-system made by Shield Diagnostics company (Great Britain). Content of von Willebrand factor was measured in percents from a standard test by the calibration curve. The normal limits of activity of von Willebrand factor are (163,80±6,33)%, that is confirmed in our researches.

The statistical analysis of the got indexes was conducted with the use of Student criterion and Pirson linear coefficient of correlation. Value of Р<0,05 was considered statistically reliable.

Research results and their discussion

The concentration of von Willebrand factor substantially changed for the patients of the first – (201,80±4,29) % and the second study group – (219,05±2,68) %, considerably exceeding the level of healthy persons – (163,80± 6,33) % (P<0,02).

The concentration of the noted index was increased reliably (Р_II-I<0,05), with the extent of immunodeficiency progress.

The middle reverse correlation between the amount of T-lymphocytes/helpers and between the amount of T-lymphocytes/helpers and concentration of von Willebrand factor (r=-0,43...-0,68) was studied.

A high level of von Willebrand factor for the examined patients, obviously, is due to damage of the structure of the circulatory system of the organism, because of ability HIV to cause the direct damage of endothelium.

Consequently, findings confirm a hypothesis about development of endothelium disfunction at HIV/AIDS and dictate the necessity of clinical approbation of efficiency of endothelium protectors for the complex treatment.

Conclusions

1. HIV/AIDS is accompanied by disfunction of endothelium that testified by a substantial increase of content of von Willebrand factor in the patient blood.

2. Concentration of von Willebrand factor in the the patient blood in III-IV the stages of HIV/AIDS considerably higher, than in the I-II stages.

3. HIV/AIDS is accompanied by decreased amount of leukocytes, T-cell and T- lymphocytes/helpers in peripheral blood.

4. The reverse correlation between the amount of T-lymphocytes and content of von Willebrand factor (r=-0,88...-0,43) was studied.

5. The development of endothelium disfunction at HIV/AIDS dictates the necessity of clinical approbation of efficiency of endothelium protectors for the complex treatment.

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