Clinical significance of the humoral immune response to modified LDL

Lopes‐Virella, Maria F.; Virella, Gabriel

doi:10.1016/j.clim.2009.04.001

Cited by 73 publications

(61 citation statements)

References 116 publications

(167 reference statements)

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“…Most forms of modified LDL are immunogenic and induce autoantibody production; these proinflammatory properties are greatly increased by the formation of LDL-containing immune complexes. 8 This adaptive immune response to modified LDL has also been reported in mice. 9 Patients with type 1 diabetes have elevated serum levels of antibodies, predominantly IgG against proteins modified by glycoxidation or lipoxidation, including oxidized LDL, malondialdehyde-modified LDL, and advanced glycation end products-modified LDL, 10,11 even though these patient cohorts do not have the excessively increased hypercholesterolemia that is typical in patients with type 2 patients.…”

supporting

confidence: 52%

“…Furthermore, LDL size, susceptibility to oxidation, and lipid fatty acid composition are critical in the formation of immune complexes in type 2 diabetic patients. 8 Indeed, oxidized LDL-containing immune complexes represent a good marker to evaluate the effect of humoral immunity in diabetes complications. 8,11,12 At sites of injury, IgG immune complexes are recognized by infiltrating and resident cells through specific receptors for the Fc region (FcgRs).…”

mentioning

confidence: 99%

“…8 Indeed, oxidized LDL-containing immune complexes represent a good marker to evaluate the effect of humoral immunity in diabetes complications. 8,11,12 At sites of injury, IgG immune complexes are recognized by infiltrating and resident cells through specific receptors for the Fc region (FcgRs). 13,14 In mice, four different classes of FcgRs are described (FcgRI/CD64, FcgRIIb/CD32, FcgRIII/CD16, and FcgRIV), which differ by their distinct affinity, cellular distributions, and effector functions.…”

mentioning

confidence: 99%

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Fcγ Receptor Deficiency Attenuates Diabetic Nephropathy

López-Parra

Mallavia

López-Franco

et al. 2012

Journal of the American Society of Nephrology

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Among patients with diabetes, increased production of immunoglobulins against proteins modified by diabetes is associated with proteinuria and cardiovascular risk, suggesting that immune mechanisms may contribute to the development of diabetes complications, such as nephropathy. We investigated the contribution of IgG Fcg receptors to diabetic renal injury in hyperglycemic, hypercholesterolemic mice. We used streptozotocin to induce diabetes in apolipoprotein E-deficient mice and in mice deficient in both apolipoprotein E and g-chain, the common subunit of activating Fcg receptors. After 15 weeks, the mice lacking Fcg receptors had significantly less albuminuria and renal hypertrophy, despite similar degrees of hyperglycemia and hypercholesterolemia, immunoglobulin production, and glomerular immune deposits. Moreover, diabetic Fcg receptor-deficient mice had less mesangial matrix expansion, inflammatory cell infiltration, and collagen and a-smooth muscle actin content in their kidneys. Accordingly, expression of genes involved in leukocyte infiltration, fibrosis, and oxidative stress was significantly reduced in diabetic kidneys and in mesangial cells cultured from Fcg receptor-deficient mice. In summary, preventing the activation of Fcg receptors alleviates renal hypertrophy, inflammation, and fibrosis in hypercholesterolemic mice with diabetes, suggesting that modulating Fcg receptor signaling may be renoprotective in diabetic nephropathy.

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supporting

confidence: 52%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Fcγ Receptor Deficiency Attenuates Diabetic Nephropathy

López-Parra

Mallavia

López-Franco

et al. 2012

Journal of the American Society of Nephrology

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“…Controversial findings make it uncertain if antibodies are directly expressed in a deleterious environment, or if they are a protective response of the organisms against the atherogenic particles. Some studies indicate an association between high levels of antibodies anti-LDL(-) or anti--LDLox, and CVD (30,31), whereas other found an opposite relationship (32,33). Part of the controversy has been explained by the formation of immunocomplexes and/or other factors that interfere in the laboratory measurement of the antibodies (34).…”

Section: Emerging Cardiovascular Risk Markers Associated To Lipid Metmentioning

confidence: 99%

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

Silva

Almeida-Pititto

Ferreira

2015

Arch. Endocrinol. Metab.

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There are numerous particles, enzymes, and mechanisms in the lipid metabolism that are involved in the genesis of cardiovascular disease (CVD). Given its prevalence in populations and its impact on mortality, it is relevant to review the lipid metabolism as it may potentially provide subsidies to better prediction. This article reviews the importance of traditional cardiovascular risk factors and comments on the potential of novel lipid biomarkers involved in the physiopathology of CVD. The Framingham cohorts proved the role of traditional risk factors (physical inactivity, smoking, blood pressure, total cholesterol, LDL-C, HDL-C, plasma glucose) in the prediction of cardiovascular events. However, a significant number of individuals that suffer from a cardiovascular event has few or none of these factors. Such finding indicates the need for new biomarkers able to identify plaques that are more susceptible to rupture. Some of bloodstream biomarkers related to lipid metabolism are modified LDL particles, apolipoprotein AI (apo AI), apolipoprotein B, lipoprotein (a) [Lp (a)], cholesteryl ester transfer protein (CETP), subtypes of LDL and HDL particles, and lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). These factors participate in the atherosclerotic process, and are abnormal in individuals at high risk, or in those who suffered from a cardiovascular event. Lp (a) determination is already employed in clinical practice and should be included as a reference parameter for CVD monitoring. Furthermore, there are expectations for wider use of apo B, non-HDL cholesterol and total cholesterol / HDL-C determination to improve cardiovascular risk assessment. Arch Endocrinol Metab. 2015;59(2):171-80

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“…Another mechanism of cytotoxicity is the high content of lysophosphatidylcholine in oxLDL that disrupts the integrity of cytoplasmatic membrane and promotes cell death (Naito, 1994). OxLDL is immunogenic, and autoantibodies against oxidation-specific epitopes are detected in normal and hyperlipemic subjects (Lopes-Virella & Virella, 2010). The role of these autoantibodies is not well defined and published results are divergent; positive or negative associations between autoantibodies and atherosclerosis have been reported.…”

Section: Oxidative Modification Of Ldlmentioning

confidence: 99%