Oxidized Low Density Lipoproteins in Patients With Transplant-Associated Coronary Artery Disease

Holvoet, Paul; Stassen, Jean–Marie; Cleemput, Johan Van; Collen, Désiré; Vanhaecke, Johan

doi:10.1161/01.atv.18.1.100

Cited by 163 publications

(111 citation statements)

References 38 publications

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“…First, oxLDL Ab may eliminate oxLDL particles from the circulation and prevent them from reentering the arterial wall. We 21 and others 34,35 have shown that oxLDL is detectable in human plasma at a very low concentration. We recently found that oxLDL Ab titer correlated inversely with plasma oxLDL concentration in a healthy population.…”

Section: Discussionmentioning

confidence: 62%

Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Fukumoto

Shoji

Emoto

et al. 2000

ATVB

124

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Abstract-Oxidation of LDLs plays an important role in atherosclerosis, and immune response to oxidized LDL (oxLDL) may modulate atherogenesis. Although immunization with oxLDL is shown to suppress atherogenesis in animal models, the role of the immune response to oxLDL is not well established in humans. We investigated the relationship between the titer of anti-oxLDL antibody (oxLDL Ab) and arterial wall thickness in a healthy population with no clinical signs of atherosclerosis. Intima-media thickness of the carotid arteries (CA-IMT) was measured by high-resolution B-mode ultrasonography in 446 healthy subjects. The titer of IgG-class oxLDL Ab was measured by a solid-phase ELISA. In univariate analysis, CA-IMT correlated positively with age, systolic blood pressure, total cholesterol, triglyceride, LDL cholesterol, body mass index, and waist-to-hip ratio, whereas it correlated negatively with HDL cholesterol and oxLDL Ab titer. The inverse association between oxLDL Ab titer and CA-IMT remained significant in multiple regression analysis, which took other confounding variables into account. These results indicate an independent inverse relationship between oxLDL Ab titer and CA-IMT in healthy subjects, supporting the hypothesis that immune response to oxLDL may have a protective role at an early stage of human atherosclerosis.

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Section: Discussionmentioning

confidence: 62%

Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Fukumoto

Shoji

Emoto

et al. 2000

ATVB

124

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“…42,44,45) Due to experimental differences, the actual values cannot be directly compared to each other. However, it is reasonable to believe that the various studies clearly indicate the involvement of oxidative modification of LDL in these clinical conditions.…”

Section: Oxldl and Various Diseasesmentioning

confidence: 99%

Oxidized Low-density Lipoproteins: What Is Understood and What Remains to Be Clarified.

Itabe

2003

Biological & Pharmaceutical Bulletin

128

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Oxidized low-density lipoprotein (OxLDL) has previously been thought to promote atherogenesis through foam cell formation. However, the actual nature of OxLDL present in vivo remained obscure until recently. We have produced a monoclonal antibody, DLH3, which specifically binds to OxLDL but not to native LDL. The presence of OxLDL in the LDL fraction of human plasma was demonstrated by introducing a sandwich ELISA procedure using DLH3 together with an anti-apoB antibody. Furthermore, OxLDL levels appeared to increase in certain pathological conditions including acute myocardial infarction and carotid artery atherosclerosis. Accumulation of OxLDL in atherosclerotic lesions has also been demonstrated by immunohistochemical and biochemical studies using the DLH3 antibody. This antibody recognizes oxidized phosphatidylcholines (OxPC) generated during oxidative modification of LDL, and OxPC-apoB adducts formed in OxLDL are the presumed antigens. Measuring OxLDL in plasma would be a useful diagnostic tool for cardiovascular diseases. However, there still remain some major questions related to OxLDL, the answers to which are crucial for understanding the mechanisms of atherogenesis.Key word atherosclerosis; oxidized low-density lipoprotein (LDL); foam cell; oxidized phosphatidylcholine; macrophage contact. A mesh-shaped sheet of elastin called elastic lamina lies between the endothelial cells and the layers of smooth muscle cells. There is accumulation of collagen fibers and lipids, and invasion of various cells including macrophages between the endothelial cells and the elastic lamina in the earliest stages of atherosclerotic lesions, which is referred as to as diffuse intimal thickening (Fig. 1b). Fatty streaks are macroscopic lumps on the vessel walls which coalesce to form long lesions. In this stage, there is massive acculumation of lipids in intimal areas and large numbers of macrophage-derived foam cells are found. Some foam cells are generated from smooth muscle cells (Fig. 1c). Fibrous caps are formed with smooth muscle cells and numerous fibrous proteins such as collagens are found in atheromata. In the deep regions of the atheroma, massive accumulations of macrophages, smooth muscle cells and extracellular matrix proteins are found (Fig. 1d).When the luminal surface of the atherosclerotic lesion is damaged or cracked, platelets immediately adhere and aggregate at the cracked sites and subsequently generate thrombi (Fig. 1e). Thrombus formation can lead to complete occlusion of the blood vessel, and is the primary cause of myocardial and cerebral infarction. From a number of research findings it has been presumed that atheromatous lesions enriched with lipids or foam cells become vulnerable and prone to rupture.Russel Ross proposed the so-called "modified injury-response hypothesis" as a possible mechanism of development of atheroslcerosis.22) When endothelial cells are injured or stressed, they respond to the injury by inducing various cytokines. Then, the cytokines activate other types of cells such as macr...

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“…In retrospective studies, we have demonstrated an association between angiographically detected coronary artery disease (CAD) and plasma levels of oxidized LDL. 3,4 However, the retrospective data did not allow us to conclude whether the increase of plasma levels of oxidized LDL was a consequence of the development of CAD or whether oxidized LDL was an independent risk factor of transplant CAD. The aim of the present prospective study was to assess the prognostic value of oxidized LDL for CAD.…”

mentioning

confidence: 98%

Oxidized Low Density Lipoprotein Is a Prognostic Marker of Transplant-Associated Coronary Artery Disease

Holvoet

Cleemput

Collen

et al. 2000

ATVB

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Abstract-Retrospective studies identified oxidized low density lipoprotein (LDL) in the blood as a diagnostic marker of coronary artery disease (CAD). This prospective study sought to determine the prognostic value of oxidized LDL for CAD in cardiac transplant patients. Oxidized LDL was measured in 99 cardiac transplant patients with normal coronary angiograms at baseline and was measured again after a median follow-up of 2 years at the time of a second angiogram. Key Words: lipoproteins Ⅲ transplantation Ⅲ coronary artery disease Ⅲ prognosis A n association between LDL oxidation and atherogenesis was first suggested by experiments showing that oxidized LDL caused injury to endothelial cells (reviewed in Reference 1) and was further supported by studies in animal models showing a protective effect of antioxidants against the progression of atherosclerosis (reviewed in Reference 2). In retrospective studies, we have demonstrated an association between angiographically detected coronary artery disease (CAD) and plasma levels of oxidized LDL. 3,4 However, the retrospective data did not allow us to conclude whether the increase of plasma levels of oxidized LDL was a consequence of the development of CAD or whether oxidized LDL was an independent risk factor of transplant CAD. The aim of the present prospective study was to assess the prognostic value of oxidized LDL for CAD. Because similar increases of oxidized LDL were observed in patients with cardiac transplant vasculopathy and in patients with ischemic heart disease and because transplant vasculopathy progresses rapidly, the role of oxidized LDL in the development of CAD was first assessed in cardiac transplant patients. Therefore, oxidized LDL was measured in 99 cardiac transplant patients with normal coronary angiograms at baseline and was measured again after a median follow-up of 2 years at the time of a second angiogram. Methods Study DesignThe cohort of the present prospective study constituted 99 of 105 potentially recruitable cardiac transplant patients: patients transplanted at least 1 year before collection of the baseline blood sample (between December 1993 and May 1996), with a normal baseline coronary angiogram and a follow-up angiogram at least 2 years later. The baseline angiogram was obtained at a median of 36 months (12 to 84 months) after transplantation. The median of follow-up was 24 (range 24 to 36) months.All coronary angiograms were assessed by 2 angiographers (J.V.C. and J.V.), who where unaware of the oxidized LDL levels. Angiograms were visually graded as follows: grade 0, normal coronary arteries; grade 1, minor abnormalities with Ͻ50% stenosis of primary or secondary branches and normal left ventricular function; and grade 2, Ն50% stenosis of primary or secondary branches or distal involvement with impaired left ventricular function. Seventy-eight patients still had angiographically normal coronary arteries (controls), whereas 21 showed angiographically detectable atherosclerotic lesions in the coronary arteries (cases). All cases ha...

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Oxidized Low Density Lipoproteins in Patients With Transplant-Associated Coronary Artery Disease

Cited by 163 publications

References 38 publications

Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Antibodies Against Oxidized LDL and Carotid Artery Intima-Media Thickness in a Healthy Population

Oxidized Low-density Lipoproteins: What Is Understood and What Remains to Be Clarified.

Oxidized Low Density Lipoprotein Is a Prognostic Marker of Transplant-Associated Coronary Artery Disease

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