[The Study of Biochemical Factors of Calcification of Stable and Unstable Plaques in the Coronary Arteries of Man].

OBJECTIVE: The aim of the study was to study biochemical factors of calcification in stable and unstable plaques of coronary arteries and in the blood of patients with severe coronary atherosclerosis, to find associations of biochemical factors of calcification with the development of unstable atherosclerotic plaque. MATERIALS AND METHODS: The study included 25 men aged 60,4±6,8 years who received coronary bypass surgery. In the course of the operation intraoperative indications in men were from coronary endarteriectomy (s) artery (a - d) and histological and biochemical analyses of the samples of the intima / media. Out of 85 fragments of intima / media of coronary arteries, 15 fragments of unchanged intima / media, 39 fragments of stable atheromatous plaque and 31 fragments of unstable plaque were determined. In homogenates of samples of intima / media (after measurement of protein by the method of Lowry) and in blood by ELISA were determined by biochemical factors of calcification: osteoprotegerin, osteocalcin, an osteopontin, osteonectin, as well as inflammatory factors (cytokines, chemokines). RESULTS: A significant direct correlation (Spearman coefficient =0.607, p<0.01) between the stages of atherosclerotic focus development to unstable plaque and the degree of calcification of atherosclerotic focus development samples was found. There was an increased content of osteocalcin in stable and unstable plaques by 3.3 times in comparison with the unchanged tissue of intima / media of coronary arteries, as well as in samples with small and dust-like, with coarse-grained calcifications in comparison with samples without calcifications by 2.8 and 2.1 times, respectively. According to multivariate logistic regression analysis, the relative risk of unstable atherosclerotic plaque in the coronary artery is associated with a reduced content of osteocalcin (OR=0.988, 95 % CI 0.978-0.999, p=0.028). Also, the relative risk of calcifications in the atherosclerotic plaque in the coronary artery is associated with an increased content of osteocalcin (OR=1,008, 95 % CI 1,001-1,015, p=0,035). In men with severe coronary atherosclerosis, a significant inverse correlation was found (Spearman coefficient -0.386, p=0.022) between the content of osteoprotegerin in the vascular wall and in the blood.

Association of some hemostasis and endothelial dysfunction factors with probability of presence of vulnerable atherosclerotic plaques in patients with coronary atherosclerosis.

OBJECTIVE: The study was dedicated to investigation of some hemostasis and endothelial dysfunction factors association with probability of presence of vulnerable atherosclerotic plaques in coronary arteries in men with atherosclerosis. RESULTS: The blood levels of factor VII, factor XII and MCP-1 were higher, and concentration of sVCAM-1 lower in men with vulnerable atherosclerotic plaques in the coronary arteries, compared to men who had stable plaques. Have been revealed correlation links between the blood levels of factor II, factor XII, MCP-1 and the presence of vulnerable atherosclerotic plaques in the coronary arteries. Results of logistic regression analysis showed that the relative risk of present of vulnerable atherosclerotic plaques in the coronary arteries is associated with an elevated blood level of factor XII and MCP-1.

Immunohistochemical Features of Different Types of Unstable Atherosclerotic Plaques of Coronary Arteries.

We performed a complex morphological study of samples of different types of unstable atherosclerotic plaques obtained from 33 men with occlusive coronary atherosclerosis, who underwent coronary artery endarterectomy during coronary artery bypass surgery. In the samples, expression of MMP-2 and MMP-9, collagen IV, CD31, CD34, factor VIII, and actin of smooth muscle cells was evaluated by morphometric and immunohistochemical methods. The maximum expression of MMP-9 was found in unstable plaques of the lipid type, where it 1.4- and 1.24-fold surpassed the corresponding levels in plaques of the inflammatory-erosive and degenerative-necrotic types. Unstable plaques of the degenerative-necrotic type are characterized by the most intensive expression of collagen IV in comparison with plaques of the inflammatory-erosive and lipid types (by 2.8 and 2.2 times, respectively). The maximum neovascularization was detected in inflammatory-erosive plaques, which was confirmed by enhanced expression of CD31 and CD34 markers in comparison with plaques of the lipid (by 7.6 and 18.95 times, respectively) and degenerative-necrotic (by 31.1 and 39.8 times) types.

Immunohistochemical Phenotypes of Stable and Unstable Occlusive Atherosclerotic Plaques in Coronary Arteries.

We performed a complex morphological analysis of atherosclerotic plaques obtained from 68 men with coronary atherosclerosis during coronary bypass surgery with endarterectomy. The expression of MMP-2 and MMP-9, collagen IV, CD31, CD34, factor VIII, and of smooth muscle cell actin was measured in the samples by morphometric and immunohistochemical methods. The expression of MMP-2 and MMP-9 as well as the intensity of neoangiogenesis estimated by the expression of CD31, CD34, and factor VIII in unstable plaques was significantly higher than in stable ones. Immunohistochemical analysis showed more intensive collagen IV expression in stable plaques. The observed differences in immunohistochemical phenotypes of stable and unstable atherosclerotic plaques reflect peculiarities of morphogenesis of atherosclerotic foci in the coronary arteries determining their further development.

[Changes of Content of Matrix Metalloproteinases and Their Tissue Expression in Various Types of Atherosclerotic Plaques].

AIM: to investigate diagnostically significant for atherosclerotic plaques (ASP) of various types parameters of activity of matrix metalloproteinases (MMP-3, MMP-7, MMP-9) in homogenates, as well as tissue expression of MMP-2, MMP-9 and collagen type IV. MATERIALS AND METHODS: We included in this study 54 men with coronary atherosclerosis without acute coronary syndrome who underwent coronary artery bypass surgery with endarterectomy. In the obtained samples we determined levels of MMP-3, MMP-7, and MMP-9 (by enzyme immunoassay), as well as tissue expression of antibodies to MMP-2, MMP-9 and collagen type IV. RESULTS: In unstable plaques we observed increased activity of MMP-7 and MMP-9, significant increase of tissue expression of MMP-2 and MMP-9, and decreased expression of type IV collagen. Of three types of unstable ASP the highest tissue expression of MMP-9 was found in plaques of lipid type compared with plaques of necrotic and inflammatory-erosive types. Expression of type IV collagen predominated in plaques of necrotic type. CONCLUSION: The data obtained allows us to speak about tissue expression of collagen as the marker of fibrous cap stability; the presence of metalloproteinases in necrotic detritus, collagen fibers, and cellular elements can characterize an ASP as unstable or being in the transitional structural state. The immunohistochemical method helps to detect structural elements that characterize instability in various types of ASP.

Associations of Osteocalcin, Osteoprotegerin, and Calcitonin with Inflammation Biomarkers in Atherosclerotic Plaques of Coronary Arteries.

We studied associations of osteocalcin, osteoprotegerin, and calcitonin with markers of inflammation in atherosclerotic plaques in coronary arteries and assessed the influence of these biomolecules on calcification of atherosclerotic plaques. The initial stage of calcification of atherosclerotic plaques is characterized by activation of inflammatory processes, which is seen from increased levels of proinflammatory biomarkers (IL-6, IL 8, TNF-α, and IL-1ß). Progressive calcification of atherosclerotic plaques is accompanied by insignificant accumulation of calcitonin and osteoprotegerin. The exception is osteocalcin, its concentration significantly increased during calcification. The results suggest that severe vascular calcification can be regarded as non-specific marker of atherosclerosis. Instability of atherosclerotic plaques is associated with higher level of calcification.

Ultrastructural and metabolic features of stress-adaptive rearrangements of myocardium in infants after surgery-induced up-regulation of lipoperoxidation processes.

Surgical correction of complicated congenital heart disease in infants is terminated by postischemic reperfusion of myocardium accompanied with closure of more than 20% microvessels in the coronary bed by edematous endothelial cells, their bleb-like fragments, and aggregates of the blood formed elements. Degradation of the transmission capacity of the coronary microvessels developed in parallel with moderation of activity of the antiradical protection enzymes and positively correlated with the level of LPO secondary products, whose elevation during the surgery stages was not reduced by catalase activation.