Autoantibodies to OxLDL Are Decreased in Individuals With Borderline Hypertension

Wu, Ruihua; Fairé, Ulf dé; Lemne, Carola; Witztum, Joseph L.; Frostegård, Johan

doi:10.1161/01.hyp.33.1.53

Cited by 109 publications

(82 citation statements)

References 51 publications

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“…The oxLDLAb titer was not raised in patients with heterozygous familial hypercholesterolemia compared with matched control subjects 34 ; it was lower in smokers than in nonsmokers, 35 and in patients with borderline arterial hypertension than in matched normotensive control subjects. 31 Moreover, the oxLDLAb titer did not show any differences between men with established hypertension in the ELSA study and normotensive control subjects, nor did it show any association with carotid atherosclerosis. 36 Despite the evidence involving oxLDL in atherosclerosis, 1,6 the mechanisms associated with formation of antibodies to oxLDL have not been widely investigated.…”

Section: Discussionmentioning

confidence: 77%

“…9 High plasma levels of oxLDLAbs have also been associated with carotid artery plaque instability in another study of Japanese patients, 30 but conflicting results on the association with carotid atherosclerosis exist in whites. 15,31 A more recent study, in which the ethnicity of case and control subjects was not specified, showed higher IgG oxLDLAb titer in 8 patients with acute MI, compared with 15 patients with unstable angina, 17 patients with stable CAD, or 8 subjects with normal coronary arteries. 32 However, higher IgM oxLDLAb titers and higher IgM LDL immune complexes were observed in the normal subjects than the other groups.…”

Section: Discussionmentioning

confidence: 99%

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Antibodies to Oxidized Low-Density Lipoproteins and Angiographically Assessed Coronary Artery Disease in White Patients

et al. 2003

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Background-Low-density lipoprotein (LDL) can be oxidatively modified by reactive oxygen species, thus generating oxLDL. The latter induce formation of specific antibodies (oxLDLAb), which are detectable in patients with atherosclerosis, in which they might play a pathogenic or a protective role. Thus, we aimed to investigate the association of antibodies with oxidized LDLs (oxLDL) (oxLDLAbs) with coronary artery disease (CAD) and acute coronary syndromes. Methods and Results-In a cross-sectional study of 529 consecutive patients undergoing quantitative coronary angiography for suspected CAD, we measured the titer of IgG oxLDLAbs by ELISA. With regression analysis techniques, we also investigated the determinants of oxLDLAb titer and the association of oxLDLAbs with CAD severity. We found no significant differences of oxLDLAb titer between groups of patients without and with different CAD severity. The oxLDLAb titer was 18.6 enzyme units (EU) (11.5 to 25.7 EU/mL) (mean, 95% CI) in patients without CAD; 16.8 EU (9.6 to 24.2 EU) in patients with stenosis Ͻ50%; and 19.9 EU (15 to 24.8 EU), 17.2 (13.8 to 20.6 EU), and 14.7 EU (12.1 to 17.3 EU) in those with in 1-, 2-, or 3-vessel Ն50% stenosis, respectively. Similarly, no differences of oxLDLAb titer between patients without and with acute coronary syndrome were found. The oxLDLAb titer correlated weakly with aging and with serum total, LDL, and HDL cholesterol and plasma homocysteine levels; however, only age and HDL cholesterol remained significant predictors of the oxLDLAb titer at a stepwise regression analysis. Conclusions-The results of this study, which was adequately powered from the statistical standpoint, provided no evidence for an association of IgG oxLDLAb titer with angiographically assessed CAD in whites. (Circulation. 2003; 108:2467-2472.)

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Antibodies to Oxidized Low-Density Lipoproteins and Angiographically Assessed Coronary Artery Disease in White Patients

et al. 2003

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“…The results of these studies were rather disappointing, because the results were often conflicting and failed to produce a clear cut indication of the clinical value of modified lipoprotein antibody assays as biomarkers for the development and/or progression of atherosclerosis. While some groups reported a positive correlation between the levels of oxLDL antibodies and different endpoints considered as evidence of atherosclerotic vascular disease, such as progression of carotid atherosclerosis or risk for the future development of myocardial infarction [21][22][23][24][25][26][27], others failed to show such correlation or showed an inverse correlation [28][29][30][31][32][33][34][35][36][37][38].…”

Section: Modified Lipoprotein Antibodiesmentioning

confidence: 99%

Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

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Modified forms of LDL are immunogenic and activate both cell-mediated and humoral immune responses. Both types of responses are pro-inflammatory and are probably primary players in the perpetuation of the chronic inflammatory reaction characteristic of atherosclerosis. The immunologic response to modified LDL can be directed to MHC-II-associated peptides in the case of T helper cells, and to a variety of epitopes -modified lysine groups, modified phospholipids, proteins that become associated with oxidized LDL (such as β2GP1) -in the case of B cell responses. T cell activation is likely to play a major role through cross-activation of macrophages. Humoral responses to modified LDL are pathogenic as a consequence of the formation of antigen-antibody complexes containing modified LDL and IgG antibodies. Those immune complexes induce cholesterol ester accumulation in macrophages and macrophage-like cells, and induce the release of proinflammatory cytokines, chemokines, oxygen active radicals, and matrix metalloproteinases from those cells. There is no conclusive evidence supporting a protective role for IgM antibodies in humans, possibly because autoantibodies to modified lipoproteins are predominantly of the IgG isotype.

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“…While some groups reported a positive correlation between the levels of free oxLDL antibodies and different endpoints considered as evidence of atherosclerotic vascular disease, progression of carotid atherosclerosis, or risk for the future development of myocardial infarction, (13)(14)(15)(16)(17)(18)(19) others failed to show such correlation or showed an inverse correlation. (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) On the other hand, there is a significant body of evidence supporting a pathogenic role for immune complexes formed by oxLDL and their corresponding antibodies (oxLDL IC), both in what concerns atherosclerosis and macrovascular disease (5;9;30-34) and nephropathy. (35;36) Recently, however, several groups have proposed a protective role for the humoral immune response to modified LDL, based on data first obtained in animal models in which the predominant istoype of oxLDL antibody is IgM.…”

Section: Introductionmentioning

confidence: 99%

Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy

Virella

Carter

Saad

et al. 2008

Clinical Immunology

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Modified lipoproteins are immunogenic and play a key pathogenic role in vascular disease. Antibodies to oxidized LDL (oxLDL) are mostly of the proinflammatory IgG 1 and IgG 3 isotypes. We measured IgG and IgM oxLDL antibodies in immune complexes (IC) isolated from 36 patients with type 1 diabetes using a nested case-control design. IgG antibodies predominated over IgM antibodies by an 8:1 ratio. IgG antibody concentrations were higher in the nephropathy cases compared to controls (p=0.09), but no significant difference was observed because of two patients included in the study who had end-stage renal disease (creatinine > 5mg/dl and glomerular filtration rate (GFR) less than 17 ml/min). After eliminating these patients from the analysis, significant positive associations of IgG antibody concentration with serum creatinine and albumin excretion rate were observed after eliminating two patients with significant renal impairment (serum creatinine > 5 mg/dl). Similarly, a negative correlation with estimated glomerular filtration rate was observed in this subsample of 34 patients. Differences in IgM antibody concentrations by nephropathy classification were not supported by the data. In conclusion, the predominance of pro-inflammatory IgG oxLDL antibodies is associated with existence of diabetic nephropathy, and a protective role of IgM antibodies could not be demonstrated.

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Autoantibodies to OxLDL Are Decreased in Individuals With Borderline Hypertension

Cited by 109 publications

References 51 publications

Antibodies to Oxidized Low-Density Lipoproteins and Angiographically Assessed Coronary Artery Disease in White Patients

Antibodies to Oxidized Low-Density Lipoproteins and Angiographically Assessed Coronary Artery Disease in White Patients

Atherogenesis and the humoral immune response to modified lipoproteins

Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy

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