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-1β). 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.
Objective: To identify associations of fatty acids (FAs) with the antioxidant enzymes in the blood of men with coronary atherosclerosis and ischemic heart disease (IHD). Methods: The study included 80 patients: control group—20 men without IHD, the core group—60 men with IHD. The core group was divided into subgroups: subgroup A—with the presence of vulnerable atherosclerotic plaques, subgroup B—with the absence of vulnerable atherosclerotic plaques. We analyzed the levels of FAs, free radicals, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the blood. Results. Patients with IHD, compared with the control group: (1) had higher levels of SOD, CAT, myristic, palmitic, palmitoleic, and octadecenoic FAs; (2) had lower levels of GPx, α-linolenic, docosapentaenoic, docosahexaenoic, and arachidonic FAs. In subgroup A there were found: (1) negative associations of SOD—with linoleic, eicosatrienoic, arachidonic, eicosapentaenoic, docosapentaenoic and docosahexaenoic FAs, positive associations—with palmitic acid; (2) positive correlations of CAT level with palmitoleic and stearic acids; (3) negative associations between of GPx and palmitic, palmitoleic, stearic and octadecenoic FAs. Conclusions: Changes in the levels of antioxidant enzymes, and a disbalance of the FAs profile, probably indicate active oxidative processes in the body and may indicate the presence of atherosclerotic changes in the vessels.
This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.
Background: This study aimed to evaluate changes in markers of calcification and of endothelial dysfunction during the development of calcification and instability of atherosclerotic plaques and to identify associations of calcification factors with the formation of unstable plaques. Methods: We analyzed 44 male patients with coronary atherosclerosis who underwent endarterectomy in coronary arteries during coronary bypass surgery. The endarterectomy material (intima/media) was examined using histological and biochemical methods, and the stability and calcification degree of atherosclerotic plaques were assessed. In homogenates of the tissue samples and in blood, concentrations of osteoprotegerin, osteocalcin, osteopontin, osteonectin, monocyte-chemoattractant protein type 1 (MCP-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin were determined by enzyme immunoassays. Results: Unstable atherosclerotic plaques proved to be calcified more frequently (80.4% of plaques) than stable ones (45.0%). Osteonectin, E-selectin, and sVCAM-1 levels were lower in unstable plaques and plaques with large calcification deposits. Osteocalcin content increased with the increasing size of the calcification deposits in plaque. Blood osteocalcin concentration directly correlated with osteocalcin concentration in atherosclerotic plaques and was higher in the blood of patients with calcified plaques in coronary arteries. Conclusions: The results provide the basis for further research on the suitability of osteocalcin as a potential biomarker of an unstable calcified atherosclerotic plaque in a coronary artery.
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.
To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries of patients with coronary atherosclerosis using quantitative proteomics. The studies involved two groups of men with coronary atherosclerosis (group 1 (St) had only stable atherosclerotic plaques; group 2 (Ns) had only unstable atherosclerotic plaques, according to histological analysis of tissue samples); the average age of patients was 57.95 ± 7.22. Protein concentrations in serum samples were determined using the PeptiQuant Plus Proteomics Kit. The identification of protein fractions was carried out by monitoring multiple reactions on a Q-TRAP 6500 mass spectrometer combined with a liquid chromatograph. Mass spectrometric identification revealed in serum samples from patients with unstable atherosclerotic plaques a reduced concentration of proteins in the blood: α-1-acid glycoprotein, α-1-antichymotrypsin, α-1-antitrypsin, ceruloplasmin, hemopexin, haptoglobin, apolipoprotein B-100, apolipoprotein L1, afamin and complement component (C3, C7, C9). Moreover, at the same time a high concentration complements factor H and attractin. The differences were considered significant at p < 0.05. It was found that the instability of atherosclerotic plaques is associated with the concentration of proteins: afamin, attractin, components of the complement system, hemopexin and haptoglobin. The data of our study showed the association of some blood proteins with the instability of atherosclerotic plaques in coronary atherosclerosis. Their potential role in the development of this disease and the possibility of using the studied proteins as biomarkers requires further research.
Цель. Изучить некоторые факторы эндотелиальной дисфункции с целью поиска их ассоциаций с факторами свертывания крови, маркерами воспаления и с наличием нестабильных атеросклеротических бляшек в коронарных артериях у мужчин с коронарным атеросклерозом. Материал и методы. У мужчин с коронарным атеросклерозом без острого коронарного синдрома исследовали в крови концентрации факторов эндотелиальной дисфункции (эндотелин 1, моноцитарный хемоаттрактантный протеин 1 типа (MCP-1), адгезивные молекулы sVCAM-1, ассиметричный диметиларгинин, гомоцистеин, ингибитор активатора плазминогена 1 типа), факторов свертывания крови (фактор II, фактор VII, фактор XII, антитромбин III), биомаркеров воспаления (фактор некроза опухоли альфа, интерлейкины (ИЛ-1-бета, ИЛ-6, ИЛ-8), С-реактивный белок). Результаты. Наличие у пациентов в коронарных артериях (КА) нестабильных атеросклеротических бляшек ассоциировалось с повышенным уровнем в крови МСР-1 (выше в 1,9 раз; p<0,05) и сниженной концентрацией sVCAM-1 (ниже в 1,4 раза; p<0,05) по сравнению с мужчинами, у которых, согласно гистологическому заключению при анализе материалов эндартериаэктомии, в коронарных артериях не было нестабильных бляшек. Наибольшее число корреляционных связей выявлено между уровнем в крови MCP-1 и концентрациями фактора VII, антитромбина III, ИЛ-8, С-реактивный белок, ИЛ-1-бета и наличием у мужчин нестабильных атеросклеротических бляшек в КА. Заключение. Полученные результаты показали, что относительный риск наличия в коронарных артериях нестабильных атеросклеротических бляшек связан с повышенным уровнем в крови МСР-1.
Цель. Изучить взаимосвязь показателей окислительно-антиоксидантного статуса, липидного и углеводного обмена и оценить влияние этих маркеров на нестабильность атеросклеротических очагов в коронарных артериях. Материал и методы. В исследование были включены 104 пациента -мужчины, средний возраст -60,74±8,1 лет, которые были разделены на контрольную (без ИбС) и основную группу с ангиографически верифицированным коронарным ате-росклерозом и ИбС. Основная группа, была разделена на 2 подгруппы. В первую были включены 38 мужчин, у которых были нестабильные атеросклеротические бляшки, во вторую -34 мужчины, у которых обнаружены только стабильные в коронарных артериях.Во всех образцах сыворотки определяли концентрацию малонового диальдегида (МдА); резистентность липопротеинов низкой плотности (ЛНП) к окислению, общую степень окислительного стресса; содержание в ЛНП ретинола, β-каротина; общий холестерин (ХС); холестерин липопротеинов высо-кой плотности (ХС ЛВП); холестерин липопротеинов низкой плотности (ХС ЛНП); триглицериды (ТГ); глюкозу; уровни С-пептида и инсулина. Статистическую обра-ботку результатов проводили в лицензионной версии программы sPss (13.0). Результаты. У мужчин с коронарным атеросклерозом по сравнению с конт-рольной группой из исследуемого комплекса липидно-липопротеиновых, углеводных и окислительно-антиоксидантных биомаркеров в крови оказались повышенными ХС ЛНП, ТГ, апоВ, соотношение апоВ/апоА, ЛП (а), С-пептид, степень окислительного стресса и снижены ХС ЛВП, ретинол, β-каротин и резистентность ЛНП к окислению. Наличие нестабильных атеросклеротиче-ских бляшек в сосудистой стенке обусловливало взаимосвязь ХС ЛВП с ТГ (р<0,01) и с резистентностью ЛНП к окислению (р<0,05). В то время как во второй подгруппе уровень ХС-ЛВП коррелировал с ХС ЛНП (р<0,01), β-каротином и ретинолом (р<0,05). При изучении взаимо связи липидного и углеводного обмена была выявлена связь уровня глюкозы с такими показа-телями как ХС ЛВП, ХС ЛНП и ТГ (р<0,01), апо В, ЛП (а) и апоВ/апоА (р<0,05). заключение. Полученные данные указывают на связь показателей липид-ного, углеводного обмена и окислительно-антиоксидантного статуса с разви-тием коронарного атеросклероза и возможностью дестабилизации атеро-склеротических очагов. Aim. To study relation of antioxidant status, lipid and carbohydrate metabolism and to evaluate the influence of these factors on coronary atherosclerotic lesions vulnerability. Material and methods. Totally, 104 men included -mean age 60,74±8,1 y., selected to control (non-Chd) and main group with angiographically verified coronary atherosclerosis and Chd. Main group was divided to 2 subgroups. The first included 38 men, who had unstable plaques, the second -34 men who had been diagnosed only stable plaques in coronary arteries. In all serum specimens we measured: malonic dialdehyde concentration (Md); oxidation resistance of low density lipoproteides (LdL), general level of oxidation stress; level of retinol, β-carotene in LdL; total cholesterol; high density cholesterol (hdL); cholesterol of low density lipo...
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