[Adiponectin in normal and atherosclerotic intima of human aorta]. / Adiponektin v normal'noi i ateroskleroticheski izmenennoi intime aorty cheloveka.

BACKGROUND: Adiponectin (AN) is a protein synthesized by adipocytes that has regulatory effects on lipid and lipoprotein metabolism, increases tissue sensitivity to insulin, and modulates endothelial functions and inflammatory response. However, its involvement in the processes of atherogenesis remains poorly understood. OBJECTIVE: To determine the localization and sources of AN in atherosclerotic and normal human aortic intima. MATERIAL AND METHODS: Immunohistochemical study was performed on sections of atherosclerotic and normal human aorta obtained during autopsy. Reverse transcription real-time PCR was performed using biopsies of para-aortic and abdominal adipose tissue, intima-media of the thoracic aorta, atherosclerotic plaques of the human carotid and femoral arteries, as well as on endothelial cells isolated from the human thoracic aorta. Transendothelial transport of AN was evaluated in a two-chamber model using a monolayer of human endothelial cell hybridoma EA.Hy926. RESULTS: It has been established that AN is present in atherosclerotic but not in normal human aortic intima. At the same time, AN ADIPOQ mRNA was not detected either in the intima media of the human aorta, nor in isolated endothelial cells of the aorta, nor in cells of atherosclerotic plaques of the carotid and femoral arteries. AN slowly penetrated the endothelial monolayer in vitro, but this transport was significantly enhanced by the action of tumor necrosis factor-alpha (TNFa). CONCLUSION: Obtained data indicate that AN is present in atherosclerotic but not in normal aortic intima. We assume that AN is not synthesized by the cells of normal and atherosclerotic arterial walls, but permeates from the plasma. Transendothelial transport of AN, like many other plasma proteins, is activated during the development of atherosclerotic lesions, apparently under the action of pro-inflammatory cytokines, in particular, TNFα.

[The role of neovascularization in the formation of an unstable human atherosclerotic plaque]. / Rol' neovaskulyarizatsii v formirovanii nestabil'noi ateroskleroticheskoi blyashki u cheloveka.

MATERIAL AND METHODS: The study material was 20 autopsy samples obtained from males aged 65 to 72 years who died from acute atherosclerotic cardiovascular insufficiency. Aortic segments (from the arch, thoracic and abdominal regions), coronary arteries and the arteries of the base of the brain (a. basilaris) were investigated; these totaled 45 tissue segments. Neovessels and cellular responses in the arterial wall were examined by hematoxylin and eosin staining. VEGF was immunohistochemically detected using a highly sensitive two-stage streptavidin-biotin method. RESULTS: In unstable atherosclerotic lesions, there were active neovascularization processes in both the fibrous cap and the underlying parts of the adventitia. These changes are usually combined with a pronounced cellular inflammatory response that can contribute to their development. Endothelial growth factor may be one of the causes of neovascularization in unstable atherosclerotic lesions. CONCLUSION: A comparative immunomorphological study in the human aorta, coronary arteries, and a. basilaris revealed active neovascularization processes in the cap and the underlying parts of the adventitia in unstable atherosclerotic lesions. The cause of this neovascularization is probably endothelial growth factor and cellular inflammatory responses.

Role of interleukin-18 in destabilization of the atherosclerotic plaque in humans.

Precise location of IL-18 in cell and tissue elements of the atherosclerotic lesions in humans and its role in destabilization of the atherosclerotic plaque were detected. The data suggested a hypothesis on indirect involvement of IL-18 in destruction of the elastic and collagen fibers in an unstable plaque due to this cytokine capacity to induce the production of IFN-γ in T cells and macrophages, this eventually leading to inhibition of collagen and elastin synthesis in smooth muscle cells of the vascular wall and to loosening of the plaque cap.

[Autoantigens involved in the pathogenesis of atherosclerosis].

Whether antigens are involved in the development of arterial atherosclerotic lesions is discussed. The complex of antigens determines the course of atherosclerotic lesion. By acting on the antigens, it is possible to prevent atherosclerosis and to induce its regression. The methodology for studying atherosclerosis and many other diseases is shown to be difficult and multifaceted and need the participation of specialists of diverse specialties in the solution of the problems associated with the treatment of atherosclerosis.

The phenotype of macrophages which are not transformed into foam cells in atherogenesis.

Electron microscopy and immunohistochemical analysis clarified the phenotype of macrophages that are not transformed into foam cells. It is suggested that cells having such phenotype are involved in the reaction of immune inflammation in fatty streaks and atherosclerotic plaques and participate in production of cytokines. These macrophages may be derivatives of monocytes/macrophages that proliferate in the subendothelial space of arteries.