Circulating oxidized LDL, increased in patients with acute myocardial infarction, is accompanied by heavily modified HDL

Abstract

Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(−)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(−) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(−) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(−) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(−) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(−) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.

Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

“…In vivo oxLDL was modified with oxidized phosphatidylcholine (oxPC) and oxidized HDL [105]. While oxLDL, recognized using the anti-oxPC antibody, was detected in several fractions including LDL(−) fractions, oxLDL in LDL(−) was threefold higher in patients with AMI than in healthy subjects [104]. Our observation is in accordance with previous studies that reported an increase in oxLDL levels in plasma samples from patients with AMI.…”

“…Moreover, LDL(−) is enriched with HDL-like particles containing apoA-I heavily modified with acrolein adducts. Electron microscopic analysis revealed that LDL(−) contains heterogeneous and aggregated subpopulations with small-sized particles, similar to HDL [104].…”

“…Most recently, we reported the characterization of in vivo-oxLDL in the LDL(−) fraction released from atherosclerotic plaques of patients with acute myocardial infarction (AMI) [104]. In vivo oxLDL was modified with oxidized phosphatidylcholine (oxPC) and oxidized HDL [105].…”

Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins

“…The presence of oxLDL in atheromatous plaques as well as in the circulation has been demonstrated immunologically, where an increase in circulating oxLDL levels was found to be associated with cardiovascular disease [ 4 , 5 , 6 , 7 , 8 ]. In addition, increased circulating oxHDL in patients with cardiovascular diseases and its accumulation in atherosclerotic lesions were also recently demonstrated [ 9 , 10 ].…”

Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

“…First of all, a large scale of clinical study must be done to validate the significance of being a novel clinical biomarker. Dr. Sanchez-Quesada and many other study groups published a variety of papers mentioning the clinical prevalence and the pathogenic mechanisms of electronegative LDL [ 103 , 104 , 105 , 106 , 107 , 108 ]. The level difference between patients and controls are comparable, and the atherogenic properties are noticeable.…”