Soluble LDL-Immune Complexes in Type 2 Diabetes and Vascular Disease

Turk, Zdenka; Šesto, Mihajlo; Skodlar, Jasna; Ferenčak, Goran; Turk, Nikša; Stavljenić-Rukavina, Ana

doi:10.1055/s-2002-26706

Cited by 13 publications

(11 citation statements)

References 15 publications

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“…It may be argued that totally conclusive data has not yet been published, but it should be recognized that several groups have reported data that support the association of LDL-IC with manifestations of atherosclerosis, such as coronary artery disease [72; 79; 80; 114], myocardial infarction [81], intima-media thickening [82], and diabetic nephropathy [83; 85]. There is a need for reliable and simple assays so that the predictive value of oxLDL can be adequately assessed.…”

Section: Discussionmentioning

confidence: 99%

“…These authors purified oxLDL and the corresponding IgG antibodies from atheromatous lesions of humans and Watanabe hyperlipidemic rabbits, thus demonstrating that the ingredients necessary for the formation of LDL-IC are present in the damaged arterial wall. Several groups, including ours, have reported a significant correlation between soluble LDL-IC and the presence of clinical and/or laboratorial evidence of cardiovascular disease [71; 72; 77; 78; 79; 80]. Lefvert et al have reported association between circulating IC measured by non-specific assays and myocardial infarction in individuals with less that 45 yrs of age [81] and found, in a prospective study, that such IC were “a strong and independent risk factor for myocardial infarction” in 50-yr-old men [61].…”

Section: Pathogenicity Of Modified Ldl Antibodies In Humansmentioning

confidence: 97%

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Clinical significance of the humoral immune response to modified LDL

Lopes‐Virella

Virella

2010

Clinical Immunology

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Human low density lipoprotein (LDL) undergoes oxidation and glycation in vivo. By themselves, oxidized LDL (oxLDL) and AGE-LDL have proinflammatory properties and are considered atherogenic. But the atherogenicity of these lipoproteins are significantly increased as a consequence of the formation of immune complexes (IC) involving autoantibodies spontaneously formed. OxLDL and AGE antibodies have been shown to be predominantly of the IgG1 and IgG3 isotypes. OxLDL antibodies are able to activate the complement system by the classical pathway and to induce FcR-mediated phagocytosis. In vitro and ex vivo studies performed with modified LDL-IC have proven their pro-inflammatory and atherogenic properties. Clinical studies have demonstrated that the levels of circulating modified LDL-IC correlate with parameters indicative of cardiovascular and renal disease in diabetic patients and other patient populations. The possibility that spontaneously formed or induced modified LDL antibodies (particularly IgM oxLDL antibodies) may have a protective effect has been suggested, but the data is unclear and needs to be further investigated.

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Section: Discussionmentioning

confidence: 99%

Section: Pathogenicity Of Modified Ldl Antibodies In Humansmentioning

confidence: 97%

Clinical significance of the humoral immune response to modified LDL

Lopes‐Virella

Virella

2010

Clinical Immunology

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“…Orekhov and coworkers reported that the level of cholesterol in isolated circulating IC, which reflects the amount of LDL-IC in circulation, correlated with the severity of coronary atherosclerosis [43,44]. Turk et al reported that the concentrations of Apo-B in circulating IC was significantly higher in patients with coronary heart disease [45]. A prospective study involving 98 diabetic subjects recruited as part of the Pittsburgh EDIC study showed that LDL-IC and oxLDL antibodies, correlated with the development of coronary artery disease [CAD] over a period of seven years, but while the correlation with LDL-IC levels was direct, the correlation with oxLDL antibody levels was inverse [37,38].…”

Section: The Pathogenic Role Of Immune Complexes Formed By Oxldl and mentioning

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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“…Orekhov and co-workers reported that the level of cholesterol in isolated circulating IC, which reflects the amount of LDL-IC in circulation, correlated with the severity of coronary atherosclerosis (16). Turk et al reported that the concentrations of ApoB in isolated serum IC, another parameter reflective of the concentration of circulating LDL-IC, was significantly higher in patients with coronary heart disease (17). Finally, a prospective study involving diabetic subjects showed that LDL-IC correlated with the development of coronary artery disease over a period of 7 years (18,19).…”

Section: Introductionmentioning

confidence: 99%