Atherosclerosis and related cardiovascular disorders remain the leading global cause of morbidity and mortality. Modified low density lipoprotein (LDL) is considered to play a crucial role in atherosclerosis development. During the past decades, several types of atherogenic LDL modification have been discovered. Desialylation was one of the atherogenic modifications observed in circulating atherogenic LDL in vivo. Sialic acid level negatively correlates with triglyceride and cholesterol contents. Desialylated LDL is small, dense and highly susceptible to oxidation, as reported for hyperlipidemic conditions. This atherogenic modification leads to increased cholesterol intake by macrophages and smooth-muscle cells, and is also associated with other pathologies, such as diabetes mellitus. Moreover, these conditions provoke damage and desialylated LDL particles may trigger autoimmune reactions in macrophages and B-cells. Key words:Desialylation, desialylated low density lipoprotein, modified low density lipoprotein, sialic acid, atherosclerosis ABSTRACTArticle history:
Existing evidence supports the significant role of oxidative stress in the endothelial injury, and there is a direct link between increased oxidative stress, and the development of endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerosis and subsequent cardiovascular disease (CVD). The overproduction of reactive oxygen species facilitates the processes, such as oxidative modification of low-density lipoproteins and phospholipids, reduction in the NOS-derived nitric oxide, and the functional disruption of high-density lipids that are profoundly involved in atherogenesis, inflammation, and thrombus formation in vascular cells. Thus, under oxidative stress conditions, endothelial dysfunction was found to be associated with the following endothelial alterations: reduced nitric oxide bioavailability, increased anticoagulant properties, increased platelet aggregation, increased expression of adhesion molecules, chemokines, and cytokines. In this review, we summarized the evidence indicating that endothelial damage triggered by oxidation can be diminished or reversed by the compounds of olive oil, a readily available antioxidant food source. Olive oil bioactive compounds exhibited a potent capability to attenuate oxidative stress and improve endothelial function through their anti-inflammatory, anti-oxidant, and anti-thrombotic properties, therefore reducing the risk and progression of atherosclerosis. Also, their molecular mechanisms of action were explored to establish the potential preventive and/or therapeutic alternatives to the pharmacological remedies available.
Recently, it has been shown that increased level of LDL-containing circulating immune complexes (LDL-CIC) possess high diagnostic significance in clinically manifested atherosclerosis, but little is known about its diagnostic and prognostic significance in early atherosclerosis. Two-years prospective study was performed in 98 asymptomatic men aged 40-74. The rate of atherosclerosis progression was estimated by high-resolution B-mode ultrasonography as the increase in intima-media thickness (IMT) of common carotid arteries. The patients with elevated baseline levels of LDL-CIC were characterized by significantly higher levels of total and LDL cholesterol as well as significantly increased mean IMT of common carotid arteries. Among all baseline lipid parameters, only LDL-CIC and LDL cholesterol were contingent with the extent of early carotid atherosclerosis (p = 0.042 and p = 0.049, respectively) and had the highest levels of relative risk and odds ratio. During the follow up, significant IMT increase was registered in 53.1 % (n = 52) patients, IMT significant reduction was observed in 21.4 % (n = 21) patients. The increased levels of LDL-CIC, total serum cholesterol and LDL cholesterol had similar prognostic significance with the respect of atherosclerosis progression. The normal level of LDL-CIC (below than 16.0 μg/ml) was the only lipid parameter that predicted the absence of carotid atherosclerosis progression for two following years at prognostic value of 78.3 %. The results of the study allow assuming that LDL-CIC level may be employed not only as a marker of early atherosclerosis, but also has a sufficient prognostic value for clinical implications.
Garlic is believed to produce beneficial changes in different cardiovascular risk factors, thus possessing antiatherosclerotic properties. The hypotensive and cholesterol-lowering effects were investigated in two studies in men with mild arterial hypertension and in men with mild hypercholesterolemia. Eight-week treatment resulted in the reduction of both systolic and diastolic blood pressure by 5.2% (P=0.008) and 4.0% (P=0.014), respectively. In hypolipidemic study, the 12-week treatment resulted in a decrease in LDL cholesterol by 11.8% (P=0.002), while HDL cholesterol increased by 11.5% (P=0.013). In men with cerebral atherosclerosis it has been demonstrated that 14-days treatment inhibited ADP-induced platelet aggregation by 25.4% (P<0.05) and increased plasma fibrinolytic activity by 22.4% (P<0.05). One more study was performed in high-risk patients to evaluate the changes of prognostic cardiovascular risk that was calculated using algorithms derived from Framingham and Muenster Studies. Twelve-months treatment lowered 10-years prognostic risk of CHD by 13.2% in men (P=0.005), and by 7.1% in women (P=0.040). Ten-year prognostic risk of acute myocardial infarction and sudden coronary death was lowered by 26.1% in men (P=0.025). The Atherosclerosis Monitoring and Atherogenicity Reduction Study (AMAR) was designed to estimate the effect of two-year treatment with garlic powder pills on the progression of carotid atherosclerosis in asymptomatic men. A significant correlation has been revealed between the changes in blood serum atherogenicity and the changes in carotid intima-media thickness (r=0.144, P=0.045). Evidence obtained from these studies as well as series of double-blinded placebo-controlled clinical trials indicates that garlic powder pills are effective for prevention of cardiovascular disorders.
2 Российский экономический университет им. Г.В. Плеханова, 117997, Москва, Стремянный переулок, 36 3 НИИ атеросклероза (Сколково), а/я №21, 121609, Москва Одним из наиболее ранних проявлений атеросклероза является вне-и внутриклеточное отложение липидов, преимущественно эфиров холестерина, в артериальной интиме. В крови человека были обнаружены модифицированные липопротеины низкой плотности (ЛНП), которые, как предполагается, и вызывают накопление липидов в артериальной стенке, то есть являются атерогенными. В предлагаемом обзоре рассмотрены функциональные особенности и роль в атерогенезе важнейших разновидностей модифицированных ЛНП: окисленных ЛНП, мелких плотных ЛНП, электроотрицательных и, особенно, десиалированных ЛНП. Атерогенные ЛНП обладают многочисленными изменениями углеводного, белкового и липидного компонентов и могут быть названы множественно-модифицированными ЛНП. Множественные модификации ЛНП происходят в плазме человеческой крови и представляют собой каскад последовательных изменений в липопротеиновой частице: десиалирование, потеря липидов, уменьшение размера частиц, увеличение поверхностного электроотрицательного заряда и т.д. Авторы склонны считать и приводят доказательства того, что именно десиалирование является ключевым и первичным звеном этих изменений и дальнейшего развития патологии в клетках интимы. Помимо внутриклеточного накопления липидов, в работе представлены механизмы усиления потенциала атерогенности множественно-модифицированных ЛНП: влияние на пролиферацию клеток и фиброз, образование циркулирующих иммунных комплексов и агрегатов ЛНП.Ключевые слова: атерогенность, атеросклероз, десиалирование, внутриклеточное накопление липидов, липопротеины низкой плотности, окисление, транс-сиалидаза
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