ApoB-100 Lipoprotein Complex Formation with Intima Proteoglycans as a Cause of Atherosclerosis and Its Possible Ex Vivo Evaluation as a Disease Biomarker

Abstract

Experimental and clinical data indicate that the initiation and progress of atherosclerosis and its clinical manifestations are first caused by circulating apoB-100 lipoproteins that enter and are retained in the arterial intima. Extracellular sulfated proteoglycans (PGs) of the intima are the retention agents. The PGs also initiate physical and biochemical lipoprotein degradation with the production of bioactive, lipid products that trigger an inflammatory response that leads to atherosclerosis. There are many simple methods for measuring abnormalities of circulating lipoproteins and their relation to atherosclerotic cardiovascular disease (ACVD). However, limited research aims to evaluate procedures that could report quantitatively about the contribution of the interaction of apoB-100 lipoprotein-arterial intima PGs to clinical manifestation of ACVD. In the present review we discuss observations indicating that simple ex vivo evaluation of the affinity of apoB-100 lipoproteins for arterial PGs and glycosaminoglycans (GAGs) can give an indication of its association with clinical manifestations of atherosclerosis. In addition, we discuss molecular and cellular aspects of the apoB-100 lipoproteins association with arterial PGs that are related to atherogenesis and that support the experimental framework behind the current “Response-to-Retention” hypothesis of atherosclerosis.

Association Between Plasma ADAMTS-9 Levels and Severity of Coronary Artery Disease

“…These lipid-retaining properties of vascular hyaluronan-binding proteoglycans are key for the development of AS. 4…”

Proteoglycan binding as proatherogenic function metric of apoB-containing lipoproteins and chronic kidney graft failure

“…Furthermore, the clinical implementation of LPBS as a biomarker is at this point difficult due to logistic challenges and lack of standardization; overcoming these represents a future challenge. With respect to the chosen assay set-up we would like to point out that, although the use of isolated LDL in proteoglycan binding studies revealed important pathophysiological information (10,22,39), the aim of our present work was to set up an assay that can be performed in large cohorts and, if proven useful, be further developed for routine clinical chemistry laboratories.…”

“…This measure gives a realistic reflection of the binding susceptibility of plasma pro-atherosclerotic lipoproteins to proteoglycans in the arterial vessel wall. More than 90% of TC that binds to lipoproteins from plasma has been shown to be associated with LDL particles (21,22).…”

Promoting athero-protective immunity by vaccination with low density lipoprotein-derived antigens

“…There is considerable evidence to suggest that one of the earliest steps in the initiation of plaque build-up is the entry into the arterial wall, by transcytosis, of atherogenic lipoproteins (apoB− 100 containing lipoproteins: LDL, VLDL, IDL, Lp(a); Fig. 1) [4][5][6]. Transcytosis of LDL through the endothelium appears to involve several molecules such as SRB-1 scavenger receptor class B type 1 (SRB-1) and guanine nucleotide exchange factor dedicator of cytokinesis 4 (DOCK4) [7].…”