Circulating oxidized low density lipoprotein, autoantibodies against them and homocysteine serum levels in diagnosis and estimation of severity of coronary artery disease

Abstract

The oxidative hypothesis of atherosclerosis proposes that oxidative modification of low density lipoprotein (LDL) plays a critical role in atherogenesis. The evaluation of LDL oxidation in vivo is therefore very important. However, data concerning the evaluation of the above biochemical marker is very limited in clinical practice. This study was conducted to test the hypothesis that plasma levels of ox-LDL reflect atherosclerosis and determine the clinical significance in the measurement of circulating ox-LDL and autoantibodies against them as well as their correlation with homocysteine and lipid parameters in the diagnosis and severity of coronary heart disease. A total of 273 individuals were examined: 41 suffering from unstable angina pectoris (UAP), 62 from stable angina pectoris (SAP) and 170 healthy control subjects. We used a sensitive method for detecting ox-LDL that is based on a direct sandwich technique (ELISA) in which two monoclonal antibodies are directed against separate antigenic determinants on the oxidized apolipoprotein-B molecule along with another enzyme immunoassay designed to determine human antibodies to oxidized LDL (anti-oxLDL) directly in serum. Total homocysteine (HCY) was evaluated by means of a fully automated fluorescence polarization immunoassay. Patients with UAP exhibited marked elevations in oxLDL levels as compared to patients with SAP (161.2 +/- 28.4 vs. 119.2 +/- 26.6, p < 0.001) and the control subjects (67 +/- 18.8, p < 0.001). The difference in oxLDL levels between patients with SAP and the control group was also statistically significant. Similarly, patients with UAP showed marked elevations in anti-oxLDL antibodies compared to both patients with SAP (602.2 +/- 62.2 vs. 510.8 +/- 50.3,p < 0.001) and control subjects (368 +/- 79.6, p < 0.001). The difference in anti-oxLDL levels between patients with SAP and the controls was also statistically significant. OxLDL levels were not correlated with age in any of the groups studied. Triglycerides, LDL-cholesterol and total cholesterol were elevated in patients with UAP as opposed to patients with SAP and the control subjects, while HDL levels were elevated in the control subjects when compared to patients with SAP and UAP. Homocysteine levels were elevated in patients suffering from UAP and SAP when compared to healthy subjects. Patients with UAP or SAP did not differ on homocysteine levels. Our findings demonstrate the presence of oxLDL in vivo, its strong association with coronary artery disease as well as with the severity of the clinical presentation.

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

“…multiple AMI, for example), only the first one was taken into account in the survival analysis. A total of 15 fatal (9 AMI and 6 strokes) and 52 non-fatal events (20 AMI,15 strokes, 11 TIA and 6 AF) were registered during follow-up.…”

“…[9][10][11] Several studies have demonstrated increased titers of antibodies recognizing oxLDL in patients with coronary, 12 cerebral 13 or peripheral artery disease, 14 suggesting that they can serve as markers of the atherosclerotic process. 13,[15][16][17] However, whether these autoimmune responses have protective or pathogenetic effects remains to be fully elucidated. In the present study we investigated if autoantibodies against p210 at the time of carotid endarterectomy (CEA) predict risk for future cardiovascular (CV) events.…”

Oxidized low-density lipoprotein and intimal medial thickness in subjects with glucose intolerance—The Chennai Urban Rural Epidemiology Study-25

“…Several mechanisms have been proposed to explain the accelerated atherosclerotic changes seen with glucose intolerance, and this includes inflammation [6,7], increased platelet activation [8,9], and oxidative stress [10]. After the initial studies by Goldstein et al [11] on modification of low-density lipoprotein (LDL) and its role in atherosclerosis, several studies have investigated the role of modified LDL as a biochemical risk factor for atherosclerosis [12][13][14][15]. Of the various modified forms of LDL, oxidized LDL (OX-LDL) has gained a lot of interest recently [13,14].…”

A human monoclonal antibody Fabreactive to oxidized LDL and carbamylated LDL recognizes human and mouse atherosclerotic lesions

“…Oxidized LDL (oxLDL) accumulates within the intramural extracellular matrix of the coronary and carotid vasculature, where it binds to macrophages (Feng et al 2010). Oxidative modification of LDL produces reactive aldehydes, phospholipids, and lipid peroxidation products such as malondialdehyde-modified LDL (MDA-LDL), a representative form of oxLDL in which oxidation occurs mainly among the free lysine amino groups of apolipoprotein B. OxLDL levels in vivo, both in plasma and in atheromatous plaques, are strongly associated with coronary artery disease progression, the vulnerability of atherosclerotic lesions to rupture, and the severity of the clinical presentation (Nishi et al 2002;Faviou et al 2005;Hiki et al 2009). Scavenger receptors on macrophages interact with oxLDL, leading to the formation of macrophage foam cells and fatty streaks, and the progression of atherosclerotic plaques (Jeon et al 2007;Osto et al 2008).…”