Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases

Abstract

Atherosclerosis is a life-long illness that begins with risk factors, which in turn contribute to the development of subclinical disease, followed by the establishment of overt cardiovascular disease (CVD). Thrombotic-occlusive complications of atherosclerosis are among the most widespread and costly health problems. Oxidized low-density lipoprotein (OxLDL) plays an important role in atherogenesis by promoting an inflammatory environment and lipid deposition in the arterial wall. As cardiovascular events occur in individuals without common risk factors, there is a need for additional tools that may help in CVD risk assessment and management. The use of biomarkers has improved diagnostic, therapeutic and prognostic outcome in cardiovascular medicine. This review elaborates on the value of circulating OxLDL as a biomarker of CVD. Three enzyme-linked immunosorbent assays (4E6, DLH3 and E06) using murine monoclonal antibodies for determination of OxLDL blood levels have been developed. However, none of these assays are currently approved for routine clinical practice. We identified studies investigating OxLDL in CVD (measured by 4E6, DLH3 or E06 assay) by searching the PubMed database. Circulating OxLDL was found to be associated with all stages of atherosclerosis, from early atherogenesis to hypertension, coronary and peripheral arterial disease, acute coronary syndromes and ischemic cerebral infarction. The results of studies investigating the usefulness of OxLDL for CVD prediction were also summarized. Furthermore, OxLDL was found to be associated with pathologic conditions linked to CVD, including diabetes mellitus, obesity and metabolic syndrome (MetS). In addition, we have addressed the mechanisms by which OxLDL promotes atherogenesis, and the effects of antiatherogenic treatments on circulating OxLDL. Finally, we highlight the evidence suggesting that lipoprotein (a) [Lp(a)] is the preferential carrier of oxidized phospholipids (OxPL) in human plasma. A strong association between OxPL/apoB level (representing the content of OxPL on apolipoprotein B-100 particles, measured by E06 assay) and Lp(a) has been determined.

Protective effect of the polarity of macrophages regulated by IL-37 on atherosclerosis

“…They thereby play an important role in the pathogenesis and progression of atherosclerosis by facilitating inflammation and lipid deposition (Trpkovic et al, 2015;Lundqvist et al, 2015). Macrophages can differentiate into the M1 and M2 types, which can be inter-transformed depending on the body's microenvironment (Medbury et al, 2014;Chen et al, 2015).…”

Atherogenic modification of low-density lipoproteins

“…В настоящее время общепризнанно, что окисленные ЛНП вызывают накопление липидов в артериальной стенке и запускают атерогенез [14][15][16]. Представления о ключевой роли окисленных ЛНП в атерогенезе основываются на следующих аргументах.…”

“…Доля гидролизованного эфира холестерина нативных ЛНП составляла 80%, доля гидролизованного 3 Н-холестериллинолеата десиалированных ЛНП составляла 40%. Для измерения скорости этерификации холестерина SMA(+) клетки инкубировали в присутствии 14 С-меченой олеиновой кислоты [22]. Было показано, что скорость этерификации холестерина в 2-3 раза выше, чем в случае нативных ЛНП.…”

“…Десиалированные ЛНП стимулировали синтез белка в 1,5-2 раза и вызывали 2-кратное величение синтеза коллагена клетками, определяемого по включению 14 С-пролина в высвобождаемую коллагеназой фракцию инкубационной среды [62]. Было продемонстрировано также, что десиалированные ЛНП, но не нативные ЛНП, оказывали стимулирующее воздействие на включение 14 С-глюкозамина в суммарную фракцию глюкозаминогликанов SMA(+) клеток интимы аорты человека [62]. Следовательно, в отличие от нативных ЛНП, десиалированные ЛНП ускоряли синтез компонентов соединительно-тканного матрикса.…”

Reduced first-phase insulin secretion increases postprandial lipidemia in subjects with impaired glucose tolerance

“…1 Such lipoproteins are prone to be oxidized and transformed into oxidized-LDL (ox-LDL), predisposing to atherosclerosis and cardiovascular disease. 2 Also, apolipoprotein B48 and apolipoprotein B100 have a delay in postprandial clearance, contributing to atherosclerosis. 3 4 In patients with insulin resistance (IR), such apolipoproteins and lipid parameters are useful markers for clinical atherosclerosis.…”