[Inflammatory-destructive biomarkers of atherosclerotic plaques instability. Study of arterial wall and blood].

Concentrations of tumor necrosis factor, interleukin 1- and its receptor antagonist, IL-6, IL-8, IL-18, IL-2, ligand of CD40 receptor (CD40L), high sensitive C-reactive protein (hsCRP), monocyte chemotactic protein -1, endothelial monocyte activating protein II, adhesive molecules (sICAM-1 and sVCAM-1), matrix metalloproteinase (MMP-3, MMP-7, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) and endothelin-1 were studied in blood and in coronary artery intima/media of men with coronary atherosclerosis without acute coronary syndrome. Blood levels of hsCRP, IL-8, IL-6 and CD40L were higher, while blood levels of sVCAM and TIMP-1 were lower in men with prevalence of unstable atherosclerotic plaques compared to men with prevalence of stable atherosclerotic plaques in coronary arteries. Blood levels of hsCRP, IL-6 and IL-8 correlated with characteristics of coronary artery atherosclerotic plaques instability.

[Dynamics of changes of blood inflammatory-oxidative biomarkers in acute coronary syndrome].

Some inflammatory cytokines and parameters of low density lipoproteins (LDL) oxidative modification were studied in blood of 250 acute coronary syndrome (ACS) patients--Siberian inhabitants, men and women with myocardial infarction (MI) or unstable angina on first, tenth and thirtieth days of disease. The inflammatory biomarkers in men and women with MI are: increased concentrations of interleukin (IL)-6, IL-8 and C-reactive protein (CRP), especially on the first day of disease. The most significant inflammatory biomarker of ACS is increased CRP level, especially in women.

[Key laboratory diagnostic biomarkers of coronary atherosclerosis].

Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation.

[Oxidized fibrinogen and its relationship with hemostasis disturbances and endothelial dysfunction during coronary heart disease and myocardial infarction].

The highest oxidative modification of fibrinogen was found in acute myocardial infarction (MI) men and it was 1.26 and 1.56 times higher in comparison with coronary heart disease (CHD) men with anamnesis of MI and with men without CHD, respectively.

[Changes in proinflammatory cytokine and destructive metalloproteinase levels during formation of unstable atherosclerotic plaque].

We studied men with coronary atherosclerosis without acute coronary syndrome and determined typical valuable parameters of inflammatory (tumor necrotic factor, antagonist of receptor to interleukin [IL] 1, IL 6, IL 8, monocytes chemotactic protein 1, endothelial monocytes activating protein II), and destructive (matrix metalloproteinase [MMP] 3, MMP 7, MMP 9, tissue inhibitor of metalloproteinase) processes at consecutive stages of formation of coronary atherosclerotic plaque: "normal intimal tissue --> lipid stain --> early stable plaque --> unstable vulnerable plaque <--> stable plaque with fibrosis", and in 3 types of unstable plaques (lipid type, inflammatory erosive type, necrotic type).

[Atherogenic oxidative and structural modification of low density lipoproteins in men with coronary atherosclerosis].

We studied parameters of structural and oxidative modification of low density lipoproteins (LDL) in 80 men aged 35 - 65 years with coronary atherosclerosis verified at coronary angiography in comparison with 80 men of the same age without ischemic heart disease. Biochemical studies included determination of parameters of lipid blood composition by enzymatic methods, subfractional LDL profile by electrophoresis in 2 - 16% gradient polyacrylamide gel, degree of oxidative modification of lipid (lipid peroxidation products) and apoprotein (carbonyl groups) components of LDL by fluorometric and spectrophotometric methods. In men with coronary atherosclerosis we revealed elevated level of small dense LDL and substantially oxidized lipid and apoprotein components of these particles.

[Activity of inflammatory-destructive changes in the process of formation of unstable atherosclerotic plaque].

We studied parameters of inflammatory (tumor necrosis factor a, antagonist of interleukin-1 receptor, interleukin-6 , interleukin-8, C-reactive protein) and destructive (matrix metalloproteinases type 3 and 9, tissue inhibitor of metalloproteinase type 1) processes in dynamics of sequential stages of development of atherosclerotic foci in coronary arteries: unchanged intimal tissue --> lipid stain/streak --> stable young plaque --> unstable vulnerable plaque with inclination to ulceration of rupture --> stable plaque with fibrosis/calcinosis, and in various types of unstable plaques in men with coronary atherosclerosis. Characteristic for unstable plaques parameters of inflammatory activity were elevated levels of interleukins (IL) 6 and 8, C-reactive protein (CRP), of destructive activity -- elevated level of metalloproteinases-9. In inflammatory erosive type of unstable plaques (lowered level of antagonist of interleukin-1 receptor and elevated level of CRP) and in lipid type (elevated levels of IL-6, IL-8 and CRP) inflammatory activity was dominating compared with necrotic type in which dominated destructive activity (elevated level of tumor necrosis factor a and lowered level of tissue inhibitor of metalloproteinase type 1).

[A procedure for determining the oxidative modification of apolipoproteins in low-density lipoproteins].

The purpose of the present study was to develop a new procedure for estimating the oxidative modification of apolipoproteins in low-density lipoproteins (LDLs). The procedure was developed to use blood serum from 153 males aged 45-65 years, including 69 patients with coronary angiography-verified coronary atherosclerosis and 84 males from a representative sample from Novosibirsk residents of the same age. The new procedure is as follows: a rapid method for isolating serum LDLs, their apolipoprotein (apoLP) protein measurement by the Lowry procedure, their precipitation, a reaction with 2,4-dinitrophenylhydrazine in 2 M HCl solution, by subsequently rinsing in the ethanol:ethyl acetate (1:1) solution, dissolving the precipitate in 8 M urea, and by determining the level of the resultant dinitrophenylhydrazones by spectrophotometry at 363 nm, followed by conversion to LDL concentration of apoLP.

[Procedure for determination of oxidative modification of plasma fibrinogen].

The purpose of the present study was to develop a new procedure for determining the oxidative modification of plasma fibrinogen. The procedure was developed to use blood plasma from 96 males aged 35-60 years who had cardiovascular diseases: 49 patients with coronary heart disease (CHD), including 16 patients with sub-acute myocardial infarction (MI), and 47 patients with arterial hypertension without CHD. The new procedure is as follows: a rapid fibrin isolating method, a reaction with 2,4-dinitrophenylhydrazine in 2 M HCl solution, by subsequently rinsing in the ethanol : ethyl acetate (1:1) solution, dissolving the precipitate in 8 M urea, and by determining the level of the resultant dinitrophenylhydrazones by spectrophotometry at 363 nm, followed by conversion to the plasma concentration of fibrinogen.

[Effect of cytoprotection on the oxidative processes and endothelial function in elderly patients with ischemic heart disease].

The aim of the study was to investigate the effects of cytoprotectional drug Mildronate ("Grindex", Latvia) on some parameters of oxidative processes and endothelial function in elderly patients with coronary heart disease (CHD). One hundred seventeen elderly CHD patients were included into controlled study. The criteria to include the patients into the study were: men and women upwards 60 years old with CHD, with heart failure FC II or III (in accord, NYHA classification), with arterial hypertension (AH), without diabetes mellitus.