Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

Abstract

In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes.

Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma

“…Elevated levels of CICs of glycoxidized LDL has been reported to be associated with retinopathy in type 1 diabetes and in the pathogenesis of atherosclerosis (6,12). In fact, modified LDL associated with the immune complexes are proinflammatory, atherogenic and accumulating evidence indicates that LDL-containing immune complexes can also serve as a biomarker for macrovascular disease in type 1 diabetes (13). Further, it is reported that a major percentage of antibodies against AGE-modified proteins were constituted by IgGs in the diabetic patients (14).…”

The biological activity of high-density lipoprotein fractions and their role in the development of cardiovascular diseases

“…ЛПВП обладают не-сколькими видами противовоспалительной активности, включая ингибирование индуцированной цитокинами экспрессии моле-кул адгезии на эндотелиальных клетках (ЭК), ингибирование ад-гезии моноцитов к эндотелию, подавление активации моноцитов путем ингибирования синтеза провоспалительных цитокинов и хемокинов, снижение активации нейтрофилов и торможение ин-фильтрации нейтрофилов в стенке артерии [44][45][46]. Противовос-палительная активность ЛПВП по отношению к ЭК и моноцитам может быть связана с извлечением липидов из этих клеток по-средством ABCA1 и ABCG1 [46].…”

Chemical composition of circulating native and desialylated low density lipoprotein: what is the difference?

“…[14,84] In 2013 Montano [85] and colleagues showed that monoclonal anti-oxLDL IgM (E06) inhibited oxLDL binding to macrophages in a dose dependent manner. Studies on LDL-CIC discovered that LDL in these complexes had atherogenic modifications, particularly LDL were small dense and had decreased sialic acid content.…”

“…[11,12] During the past decades, numerous studies confirmed that LDL modifications, such as oxidation, desialylation and enzymatic processing, play a key role in increasing cholesterol intake, and the level of multiple modified LDL correlates with the risk of CVD. [13,14] Other types of lipoproteins that are distinguished in some studies are electronegative LDL [LDL(-)] and lipoprotein (a) [Lp(a)]. The former subclass includes modified LDL with increased negative charge, which accounts for 3-5% of the total LDL in normolipidemic subjects.…”