[Chaperones and their role in atherogenesis].

The combination of HSP60-specific humoral and cellular reactions is handled as the new diagnostic sign, reflecting the risk of the development of atherosclerosis, which is independent of other classic risk factors. Chaperones are identified as important pathogen-related antigens used to design vaccines against atherosclerosis. The high evolutionary homology of HSPs raises the issue on the safety of such vaccines.

[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.

[Contemporary views on the pathogenesis of atherosclerosis].

Recent studies show that inflammation plays the key role inthe pathogenesis of atherosclerosis. Immune cells dominate at the initial stages of the atherosclerotic lesion of blood vessels. The effector molecules accelerate the progress of the lesion. This approach to the assessment of the pathogenesis of atherosclerosis makes it possible to search the ways for the prevention and suppression of immune inflammation. Nowadays vaccination against primary autoantigens is being successfully used for protection from experimental atherosclerosis. Modulation of immune response, involved in atherosclerosis, includes vaccination inducing immune protecting response of the development of tolerance by means of the process from Th1 to Th2 cell response.

[Autoimmune and inflammatory mechanisms of atherosclerosis development].

This paper contains the results of researches from the N.N.Anichkov laboratory of atherogenesis, the analysis of initial stages of,atherosclerosis made from the position of immune inflammation in the arterial wall. The leading role of mLDL, which are the main cholesterol carrier, in the development of immune inflammation in situ is shown.

Myocardial tissue damage in rabbits injected with group A streptococci, types M1 and M22. Role of bacterial immunoglobulin G-binding surface proteins.

Acute rheumatic fever (ARF) and acute poststreptococcal glomerulonephritis (APSGN), two important sequelae of streptococcal throat or skin infections, according to current concepts may be elicited by autoimmune mechanisms due to molecular mimicry between group A streptococci (GAS) and human tissue. In the case of APSGN, however, our experimental data have indicated that GAS immunoglobulin-binding surface proteins (IgG BPs) might be of pathogenic significance by triggering anti-IgG production and immune complex formation leading to renal damage. Thus, rabbits injected with IgG-binding, as opposed to non-binding, GAS strains were found to develop renal deposition of IgG and complement factor C3 and inflammatory and degenerative glomerular changes resembling the picture seen in APSGN. In the present study, cardiac tissue material from rabbits injected with GAS was investigated. After 8 or more weeks of intravenous (i.v.) injections, minimal changes were seen in those animals receiving an IgG non-binding GAS strain, type T27, whereas those animals receiving either of two IgG-binding GAS strains, types M1 or M22, developed strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence of streptococcal IgG-binding activity. Our results demonstrate that myocardial tissue changes may be induced in the rabbit by i.v. injection of whole heat-killed GAS of at least two M serotypes. Conceivably, induction of immune complexes by bacterial IgG BPs may lead to myocardial deposition of IgG, in turn triggering a series of events, involving the complement system and proinflammatory cytokines, with resulting tissue damage. Though many virulence factors may be involved in the development of ARF and APSGN, and a given GAS strain will never cause both, our results may suggest a new pathogenetic mechanism common to these two major non-suppurative complications.

[Atherogenesis as an immunoinflammatory process]. / Aterogenez kak immunovospalitel'nyi protsess.

The paper contains findings, obtained at the laboratory of atherosclerosis of Anichkov's Research Institute of Experimental Medicine, Russia's Academy of Medical Sciences, during the last decade with the above research results being compared with published data. Atherogenesis is discussed from the standpoint of the development of immune inflammation in the arterial wall. The mechanisms and factors triggering the chain of immunoinflammatory reactions, which provoke and keep up the inflammatory process, are also under discussion. The results are indicative of that the atherosclerosis pathogenesis is equally related both with mLDL and with the reaction developing in the vascular wall.

Induction of myocarditis in rabbits injected with group A streptococci.

BACKGROUND & OBJECTIVES: We have earlier proposed that group A streptococcal (GAS) immunoglobulin binding surface proteins (IgGBPs) might trigger anti-IgG production and immune complex formation leading to glomerulonephritis. In the present study, cardiac tissue material from rabbits injected with heat-killed GAS was investigated. METHODS: Rabbits were injected intravenously with 10(9) colony forming units of streptococci three times weekly for 8 wk. Cardiac tissue samples were obtained at different times and deposition of IgG, C3, TNF-alpha and IL-6 was studied. RESULTS: After 8 or more weeks of intravenous (iv) injections, minimal changes were seen in animals receiving an IgG non-binding GAS strain, type T27, whereas in those animals receiving either of two IgG binding GAS strains, types M1 or M22, strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3 were noted. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence streptococcal IgGBPs. INTERPRETATION & CONCLUSION: The present data supported a role of streptococcal IgGBPs in the induction of myocardial tissue injury by GAS.

[Chlamydia pneumoniae as a pathogenetic risk factor in the development of arteriosclerosis and its complications]. / Chlamydia pneumoniae kak patolgeneticheskii faktor riska v razvitii ateroskleroza i ego oslozhnenii.

The literature data and the results of the authors' experiments allow one to consider Chlamydia pneumoniae as one of the leading risk factor of development of atherosclerosis and ischemic heart disease. Features of atherosclerosis morphogenesis in the presence of Chlamydia are described. Data, showing similarity of cell reactions, characterizing immune inflammation in mLDL deposit in arterial wall and obligate parasites are described. Synergism in the action of mLDL and chlamydial infection may induce a "malignant" course of atherogenesis promoting thrombosis and ischemic heart disease excerbation.

Cytotoxic effect of low-density lipoproteins.

The cytopathogenic effect of various modified lipoproteins on cultured peritoneal macrophages was studied in vitro. After minor peroxide modification lipoproteins induced apoptosis of macrophages. Immune complexes containing oxidized lipoproteins caused cell necrosis.

[Anichkov's views on the role of macrophages in atherogenesis and evolution of such views up to now]. / Evoliutsiia vzgliadov na rol' makrofagov v aterogeneze: ot N. N. Anichkova do nashikh dnei.

The appearance of macrophages in arterial wall in early morphogenesis of atherosclerosis was noted by N. N. Anichkov in 1940. The macrophages originate partly from monocytic hematogenous elements, partly from subendothelial cells. The authors show that macrophages of monocytic origin play a leading role in atherogenesis-related complex cellular-molecular alterations in the zone of arterial lesions. A cascade of cellular reactions with participation of macrophages determines a chronic course of the process by type of immune inflammation reactions with autonomic regulation.

[Current views on the pathogenesis of atherosclerosis from the position of infectious pathology]. / Sovremennye vzgliady na problemu patogeneza ateroskleroza s pozitsii infektsionnoi patologii.

The role of immune inflammation at atherogenesis is studied in the paper. Two etiological factors of atherosclerosis pathogeny are under examination: the role of modified low density lipoproteins (mLDL) and essential parasites (Chlamydia pneumoniae and Cytomegaloviruses). Generality of immune response during persistent infection into a blood vessel wall and deposit or formation of mLDL are discussed. The point of view is substantiated that the development of atherosclerotic damages of blood vessels is speeded up by a combination of the two mentioned etiological factors.

[The role of infection in the development of immune inflammation and pathogenesis of atherosclerosis]. / Rol' infektsii v razvitii immunnogo vospaleniia i patogeneze ateroskleroza.

Pathogenesis of atherosclerosis from the point of view of immune inflammation in the vascular wall is discussed in this review. Potential role of adenoviruses and chlamydia in the development of immune inflammation and mechanisms and transport of infectious agents into the vascular wall and their influence on the cell kinetics are reviewed.

[Atherogenesis as a reflection of immune inflammation in the vascular wall]. / Aterogenez kak otrazhenie razvitiia immunnogo vospaleniia v sosudistoi stenke.

Despite numerous basic and applied studies into the pathogenesis and treatment of atherosclerosis, there is no theory which could explain the development of the whole complex of changes united under the term "atherosclerosis". Examining the causes of atherosclerosis disclosed a pathogenetic association of the immunoregulatory signal CD40-CD40L with the occurrence of arterial atherosclerotic lesions. Studies of the immune mechanisms responsible for the pathogenesis of atherosclerosis (autoimmune complexes containing oxidative modification of LDL, T and B lymphocytes, inflammation mediators, hemoadhesive molecules, and immunoregulatory molecules showed the leading role of autoimmune mechanisms in atherosclerosis. The conceptual result of the studies is that the authors have elucidated the leading role of immune inflammation in the appearance and development of arterial atherosclerotic lesions. The development of a new concept of assessing the pathogenesis of atherosclerosis in the context of immune inflammation in the vascular wall opens new vistas for the treatment of this disease.