Abstract
Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis. Oxidized LDL (oxLDL) represents a variety of modification of both lipid and apolipoprotein B (apoB) components by lipid peroxidation. This promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the formation of macrophage foam cells. Recent findings also suggest that oxLDL forms complexes with β2-glycoprotein I (β2GPI) and/or C-reactive protein (CRP) within atherosclerotic lesions and that these complexes appear in the circulation. Autoantibodies (auto-Abs) against oxLDL/β2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). These autoantibodies significantly correlate with arterial thrombosis. IgG auto-Abs having similar specificity emerge spontaneously in NZW × BXSB F1 mice, which generally are considered to be an animal model of APS, and these mice produce a monoclonal IgG auto-Ab (WB-CAL-1) against oxLDL/β2GPI complexes. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/β2GPI complexes by macrophages, which suggests that such IgG auto-Abs are pro-atherogenic. In contrast, IgM anti-oxLDL natural Abs found in the atherosclerosis-prone mice have been proposed to be protective. The presence of such Abs in humans has been documented in many publications but their exact pathophysiological significance remains unclear. In this article, we review recent progress in our understanding of the clinical significance of oxidation of LDL, formation of oxLDL complexes, and Abs in atherosclerotic and/or autoimmune disease.
| Original language | English |
|---|---|
| Pages (from-to) | 558-566 |
| Number of pages | 9 |
| Journal | Autoimmunity Reviews |
| Volume | 7 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2008 |
Fingerprint
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Oxidation of LDL and its clinical implication. / Matsuura, Eiji; Hughes, Graham R V; Khamashta, Munther A.
In: Autoimmunity Reviews, Vol. 7, No. 7, 07.2008, p. 558-566.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxidation of LDL and its clinical implication
AU - Matsuura, Eiji
AU - Hughes, Graham R V
AU - Khamashta, Munther A.
PY - 2008/7
Y1 - 2008/7
N2 - Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis. Oxidized LDL (oxLDL) represents a variety of modification of both lipid and apolipoprotein B (apoB) components by lipid peroxidation. This promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the formation of macrophage foam cells. Recent findings also suggest that oxLDL forms complexes with β2-glycoprotein I (β2GPI) and/or C-reactive protein (CRP) within atherosclerotic lesions and that these complexes appear in the circulation. Autoantibodies (auto-Abs) against oxLDL/β2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). These autoantibodies significantly correlate with arterial thrombosis. IgG auto-Abs having similar specificity emerge spontaneously in NZW × BXSB F1 mice, which generally are considered to be an animal model of APS, and these mice produce a monoclonal IgG auto-Ab (WB-CAL-1) against oxLDL/β2GPI complexes. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/β2GPI complexes by macrophages, which suggests that such IgG auto-Abs are pro-atherogenic. In contrast, IgM anti-oxLDL natural Abs found in the atherosclerosis-prone mice have been proposed to be protective. The presence of such Abs in humans has been documented in many publications but their exact pathophysiological significance remains unclear. In this article, we review recent progress in our understanding of the clinical significance of oxidation of LDL, formation of oxLDL complexes, and Abs in atherosclerotic and/or autoimmune disease.
AB - Oxidative modification of low-density lipoprotein (LDL) is one of the earliest events in atherosclerosis. Oxidized LDL (oxLDL) represents a variety of modification of both lipid and apolipoprotein B (apoB) components by lipid peroxidation. This promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the formation of macrophage foam cells. Recent findings also suggest that oxLDL forms complexes with β2-glycoprotein I (β2GPI) and/or C-reactive protein (CRP) within atherosclerotic lesions and that these complexes appear in the circulation. Autoantibodies (auto-Abs) against oxLDL/β2GPI complexes occur in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). These autoantibodies significantly correlate with arterial thrombosis. IgG auto-Abs having similar specificity emerge spontaneously in NZW × BXSB F1 mice, which generally are considered to be an animal model of APS, and these mice produce a monoclonal IgG auto-Ab (WB-CAL-1) against oxLDL/β2GPI complexes. WB-CAL-1 significantly increased the in vitro uptake of oxLDL/β2GPI complexes by macrophages, which suggests that such IgG auto-Abs are pro-atherogenic. In contrast, IgM anti-oxLDL natural Abs found in the atherosclerosis-prone mice have been proposed to be protective. The presence of such Abs in humans has been documented in many publications but their exact pathophysiological significance remains unclear. In this article, we review recent progress in our understanding of the clinical significance of oxidation of LDL, formation of oxLDL complexes, and Abs in atherosclerotic and/or autoimmune disease.
UR - http://www.scopus.com/inward/record.url?scp=50949112988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50949112988&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2008.04.018
DO - 10.1016/j.autrev.2008.04.018
M3 - Article
C2 - 18625445
AN - SCOPUS:50949112988
VL - 7
SP - 558
EP - 566
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
SN - 1568-9972
IS - 7
ER -