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acad. A.N.Klimov
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Head of the department
phone: (812)234-9341 The Department was founded in 1891 by M. V. Nencki who headed it up to 1901. Later the department was headed by such outstanding biochemists as B. I. Slovtsov (1918-1924), S. S. Salazkin (1925-1931), V. S. Gulevich (1931-1932), P. A. Ashmarin, V. A. Engelgardt (1945-1951, academician of the USSR Academy of Medical Sciences (AMS) V. S. Ilyin (1951-1976), academician of RAMS A. N. Klimov(1976-1995). Since 1995 the work of the department has been headed by professor doctor of medical sciences A. D. Denisenko. The present direction of researches of the
department was laid by academician of AMS, Honored science worker of RF,
Honoris doctor of IEM A. N. Klimov in 1962 when on the initiative of
academician N. N. Anichkov he organized laboratory of lipid metabolism
in order to develop investigations in the field of atherosclerosis.
Organization of the new laboratory resulted in organization of the first
in the country wide complex of investigations of biochemical mechanisms
of the development of this disease. Later the whole of the department
under the guidance of A. N. Klimov was involved in studying lipid
metabiolism, lipoproteins and pathogenesis of atherosclerosis. In the department there are 4 laboratories:
During this period a number of great investigations were carried on which brought the department world-wide fame. One of the first achievements of the department was the evidence that lipoproteins penetrated into the vessel as a whole particle. Using different technical approaches the group of scientists under the guidance of A. N. Klimov have managed to disprove the viewpoint of a passive transfer of cholesterol from plasma lipoproteins onto some acceptors in the artery intima and to prove convincingly that the lipoprotein particle penetrates into the vessel wall as a whole and it is in the intima that it undergoes a number of metabolic changes. The using of histo- and electron-microscopic radioautography allowed to study the mechanisms and ways of transport of lipoproteins into the vessel wall. One of the greatest achievements of the Department was the development of an autoimmune theory of pathogenesis of atherosclerosis. It is based on the appearance of autoimmunogenicity in lipoproteins, formation of autoantibodies to lipoproteins and of lipoprotein-antibody autoimmune complexes. Later it was found that the cause of the development of the autoimmune response to lipoproteins was modification of lipoproteins, first of all as a result of lipid peroxidation. The data obtained allowed the development and introduction into clinical practice of two methods of treatment of atherosclerosis patients with the purpose to decrease the concentration of lipoprotein-antibody autoimmune complexes in patients' blood. In 2003 these investigations were awarded to RF State Prize in the field of science and technology (the winners of RF State Prize — A. N. Klimov, A. D. Denisenko, V. A. Nagornev).
When studying the peroxidative modification of lipoproteins it was first
established that high density lipoproteins prevent peroxidation of
atherogenic low density lipoproteins. Later the protective effect of
high density lipoproteins was confirmed in other laboratories of the
world. The laboratory of lipoproteins continues
investigating the types of modification of lipoproteins leading to the
development of autoimmune response. Recently it has been shown that
besides lipid peroxidation other modifications occur in human organism
such as acetilation, homocysteination etc. It has been found that
antilipoprotein antibodies modulate atherogenic effects of modified
lipoproteins.
Laboratory of regulation of lipid metabolism was organized in the department of biochemistry in 1997. Its main direction was the regulation of gene expression and synthesis of apolipoprotein A-1 — the main protein of antiatherogenic high density lipoproteins. The apolipoprotein A-1 gene was found to have new unknown before regulatory parts responsible for tissue-specific control of expression of this gene. In addition, approaches to the genetic correction of the impaired lipid metabolism are developed at the expense of the introduction into organism of additional copies of apolipoprotein A-1 gene with the help of non-viral methods of transfer. A new family of transcription factors was found and characterized which regulate expression of a number of genes coding the proteins involved in the lipid and lipoprotein metabolism. Laboratory of clinical lipidology organized in 1997 and working in IEM clinic deals with elaboration and approbation of new methods of diagnosis and treatment of impairments of lipid metabolism and atherosclerosis. A new method of treatment of atherosclerosis — cryoplasmaprecipitation — has been studied in detail and is widely used at present. Investigations are in progress on the gene diagnosing of the impaired lipid metabolism such as familial hypercholesterolemia, hypoalphalipoproteinemia, hypertriglyceridemia. In the
nearest future investigations will be continued to study the role of
immunological factors in the development of atherosclerosis and to
search for the ways of treatment and prophylactics of this disease
through influencing the immunological mechanisms of atherogenesis.
Investigations are planned to study the role of the genetic
predisposition to impairments of lipid metabolism and to the development
of atherosclerosis that will allow the subjects with high risk of this
disease to be detected earlier. The role of coexisting infections in
initiation and progress of atherosclerosis will be elucidated. It is
supposed to continue investigations of gene therapy of atherosclerosis. |
For
many years the N. N. Anichkov laboratory of atherosclerosis has been
headed by the academician N. N. Anichkov's disciple academician of RAMS
V. A. Nagornev. The main direction of its work is associated with the
development of N. N. Anichkov's ideas in studying patho- and
morphogenesis of atherosclerosis. Their investigations have presented a
morphological analysis of atherosclerotic alterations of the vessels
under conditions of sensibilization to lipoproteins containing
apoprotein B with the disturbed function of immune-regulating
lymphocytes. Use of a combination of scanning and transmission electron
microscopy allowed an investigation of specific properties of adhesion
of nongranulated leukocytes on the endothelium and ways of their
migration into the vessel wall at the initial and progressing stages of
atherogenesis in man. Characterization of the phenotype of macrophages
is given which are not transformed into foamy cells in atherosclerotic
lesions of the arteries but participate in presentation of autoantigens
to T-cells. A conception of the role of immune inflammation in
atherogenesis is being developed. So under investigation is not only the
vascular wall but also adjacent to it regional and distant peripheral
and central organs of the immune system. The data obtained allow the
atherosclerotic plaque to be considered as a focus of the local immune
inflammation. Under study is the role of infectious agents (bacteria and
viruses) in the development of atherosclerotic lesions of the arteries
in man.