Increased Apolipoprotein Deposits in Early Atherosclerotic Lesions Distinguish Symptomatic From Asymptomatic Patients

Abstract

Objective-Apolipoprotein E (apoE) and apolipoprotein B100 (apoB) are both involved in receptor-mediated uptake of atherogenic lipoproteins by the liver. Inefficient hepatic clearance of these lipoproteins leads to symptomatic atherosclerosis. Using arterial tissue microarrays, we tested the hypothesis that apoE and apoB accumulation in the arterial wall discriminates between patients with symptomatic atherosclerosis and patients who never experienced cardiovascular events. Methods and Results-In a postmortem study involving 49 patients (22 patients with symptomatic atherosclerosis), we quantified apolipoprotein deposits in arterial rings obtained from the left main coronary, the common carotid, the common iliac, and the renal artery applying tissue microarray technology and semiquantitative immunohistochemistry. In early atherosclerotic lesions, even before atheroma appeared, symptomatic patients had significantly more arterial apoE and apoB deposits than patients without cardiovascular events (PϽ0.001). Among the symptomatic patients, those without diabetes had more intense apolipoprotein deposits than diabetics. Large amounts of apoE and apoB were found in advanced atherosclerotic lesions, regardless of the activity of the disease. Conclusions-Increased

Associations of apolipoprotein E gene with ischemic stroke and intracranial atherosclerosis

“…23 A second mechanism may be related to the finding that apoE has proinflammatory properties. 10,24 Elevated apoE level lead to chronic inflammation that may contribute to atherosclerosis.…”

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis

“…If the apoB-48 of remnant lipoproteins lack the apoB-100 proteoglycan-binding site, how do they become retained and initiate atherogenesis? The answer lies in the finding that an otherwise cryptic domain for proteoglycan binding is un- 130 Reproduced with permission from the authors and publisher. Copyright © 2006, the American Heart Association.…”

K Domain CR9 of Low Density Lipoprotein (LDL) Receptor-related Protein 1 (LRP1) Is Critical for Aggregated LDL-induced Foam Cell Formation from Human Vascular Smooth Muscle Cells

“…In particular, LRP1 efficiently transfers cholesteryl esters (CE) from aggregated LDL (AgLDL) into human coronary VSMCs (26 -28), transforming them into foam cells (29,30). The formation of AgLDL, detected and isolated from human atherosclerotic lesions (31), is promoted through the interaction between retained LDL particles and proteoglycans in the arterial intima (32). Hypercholesterolemia, one of the major cardiovascular risk factors, strongly promotes VSMC foam cell formation by favoring LDL retention and aggregation into the arterial intima (33) but also by up-regulating LRP1 vascular levels (34).…”