Elevated Plasma Levels of Oxidized Low-Density Lipoprotein Relate to the Presence of Angiographically Detected Complex and Thrombotic Coronary Artery Lesion Morphology in Patients With Unstable Angina

Abstract

he role of inflammation in patients with acute coronary syndromes (ACS) is presently undisputed, supported by histopathological studies of unstable coronary plaque, 1 as well as clinical studies of elevated circulating acute-phase reactants. 2,3 Oxidized low-density lipoprotein (ox-LDL) is generally considered to be a key factor in the genesis of the inflammatory process in atherosclerotic lesions 4,5 and the detection of ox-LDL in human plasma has opened new avenues of the study of its relationship to the atherosclerotic process. [6][7][8][9][10] We developed a sandwich enzyme-linked immunosorbent assay (ELISA) method to measure plasma ox-LDL levels, using a specific anti-ox-LDL monoclonal antibody (DLH3) and an antiCirculation Journal Vol.71, May 2007 apolipoprotein B (apoB) polyclonal antibody. 11,12 DLH3 is specific for ox-LDL because it recognizes oxidized phosphatidylcholines (ox-PC) molecules 11 and does not bind to native, acetylated, malondialdehyde-treated, or glycated low-density lipoprotein (LDL). Using this new and highly sensitive method, we have reported that in patients with acute myocardial infarction (AMI) the plasma levels of ox-LDL are significantly higher than in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP), or in controls. 7 Recently, we also demonstrated that persistence of an increased plasma level of ox-LDL at discharge is a strong independent predictor of stent restenosis at 6-month follow-up in AMI patients. 10 UAP as a clinical diagnosis incorporates a diverse group of clinical presentations that occupy an intermediate position between the more strictly defined clinical entities of AMI and SAP. A number of previous studies have demonstrated that angiographically the culprit lesions in patients with UAP often appear irregular and contain filling defects likely to represent plaque disruption and/or plaque thrombus. [13][14][15][16] Previous clinical studies have also revealed that angiographically detected complex lesions correlated with higher Braunwald class. 17,18 However, it has also been shown that patients with Braunwald class I occasionally show angiographic evidence of a complex lesion. 17,18 Hence, given the role of ox-LDL in plaque instability in Hiroyuki Itabe, PhD † ; Toru Kataoka, MD; Yoshiki Kobayashi, MD; Anton E. Becker, MD ‡ ; Junichi Yoshikawa, MD † † ; Makiko Ueda, MD** Background Increased levels of oxidized low-density lipoprotein (ox-LDL) are related to plaque instability, so the aim of the present study was to investigate whether there is a relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) and the level of ox-LDL. Methods and ResultsPlasma ox-LDL levels were measured in 149 patients with UAP and in 88 control subjects, using a highly sensitive enzyme-linked immunosorbent assay method. Angiographic morphology of the culprit lesion was classified as either simple or complex based on the Ambrose classification. Plasma ox-LDL levels in patients with Braunwald class III were s...

Circulating oxidized low-density lipoproteins are associated with overweight, obesity, and low serum carotenoids in older community-dwelling women

“…Coronary heart disease was also associated with a higher ox-LDL/LDLcholesterol ratio, which is consistent with previous studies [2][3][4]. Women with cancer also had a higher ox-LDL/LDL-cholesterol ratio than women without cancer in this study, which is consistent with a previous study that showed elevated ox-LDL in women with breast or ovarian cancer [30].…”

“…Oxidized low-density lipoproteins (ox-LDL) are taken up by scavenger receptors on macrophages and contribute to the formation of foam cells and atherosclerotic lesions [1]. Elevated circulating ox-LDL are associated with more severe atherosclerotic lesions [2], and high circulating levels of ox-LDL have been shown to be independently predictive of subclinical atherosclerosis [3] and acute coronary heart disease [4].…”

“…Oxidized low-density lipoproteins (ox-LDL) are taken up by scavenger receptors on macrophages and contribute to the formation of foam cells and atherosclerotic lesions [1]. Elevated circulating ox-LDL are associated with more severe atherosclerotic lesions [2], and high circulating levels of ox-LDL have been shown to be independently predictive of subclinical atherosclerosis [3] and acute coronary heart disease [4].Obesity is a strong risk factor for cardiovascular disease [5]. Both abdominal obesity and general obesity (body mass index >30 kg/m 2 ) were shown to be independently associated with circulating ox-LDL among men and women, aged in Spain [6].…”

Non-Invasive Vascular Function Tests:

“…However, because the number of subjects requiring cardiovascular risk stratification is extremely large, all of the methods of morphological and functional assessment of vascular damage cannot be used in all of the subjects. Thus, the establishment of efficient strategies for risk stratification using new serological markers, 89,90 the morphological markers of vascular damage and vascular function tests (ie, selecting the best one, the best combination, or all), in addition to assessment of the risk factors for CVD, is needed.…”

LOX-1 The Multifunctional Receptor Underlying Cardiovascular Dysfunction

“…20 The plasma levels of oxLDL are related to the presence of angiographically detected complex and thrombotic lesion morphology in patients with unstable angina. 21 LOX-1 binding to oxLDL enhances nitric oxide (NO) catabolism as a result of superoxide generation, and decreases NO release via attenuated endothelial NO synthase (eNOS) activity. LOX-1 has been recently shown to form a complex with MT1-MMP under a basal condition.…”