Circulating Immune Complexes in 50-Year-Old Men as a Strong and Independent Risk Factor for Myocardial Infarction

Mustafa, A.; Nityanand, Soniya; Berglund, Lars; Lithell, Hans; Lefvert, Ann Kari

doi:10.1161/01.cir.102.21.2576

Cited by 57 publications

(39 citation statements)

References 39 publications

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“…Therefore, for functional assays of MPs, AX or other surface markerbased affinity isolation is highly recommended. 46,47 Our findings also have relevance to nonrheumatologic diseases, such as acute coronary syndrome and sickle cell disease in which the presence of circulating ICs is well documented 48,49 and may cause interference with MP detection.…”

Section: Microparticles and Protein Complexes E45mentioning

confidence: 63%

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

György

Módos

Pállinger

et al. 2011

Blood

380

410

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Numerous diseases, recently reported to associate with elevated microvesicle/ microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidinbiotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic lightscattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease. (Blood. 2011;117(4):e39-e48) IntroductionMembrane vesicles are small subcellular structures surrounded by a phospholipid bilayer. Their release by various cell types is enhanced during activation and apoptosis. 1 They represent heterogeneous structures and can be classified into several groups depending on their size, antigenic features, and mechanism of cellular release. 1 The two best characterized categories include exosomes and microvesicles/microparticles (MPs). Both populations are characterized by the exposure of phosphatidylserine, which allows annexin-V (AX) to bind to these-lipid surfaces. 1 Exosomes are composed of small, 50-to 100-nm-sized structures released on exocytosis of multivesicular bodies. 1 The diameter of MPs, formed by membrane blebbing, is described to be 100 to 1000 nm 2 . However, precise definitions of MPs are still lacking. 1,2 MPs are found in various biologic fluids, including blood plasma, 3 urine, 4 and synovial fluid (SF). 5,6 Numerous flow cytometry (FC) studies using blood plasma have shown correlation of MP counts with human cardiovascular 7 and autoimmune diseases, 8 hematologic disorders, 9 and cancer. 10 Of particular interest, autoimmune diseases were reported to be characterized by elevated levels of MPs. 11 The assessment of exosomes and MPs is complicated by the presence of further known categories of membrane bound subcellular structures, such as apoptotic vesicles, exosome-like vesicles, membrane particles, and ectosomes. 1 There is a substantial size overlap among the aforementioned vesicle categories, and the size distribution of a given vesicle preparation may also be affected by the method used for their isolation. 3,12,13 Recently, attempts have been made to standardize isolation and detection protocols for membrane vesicles. 3,14 Up until now, no systemat...

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Section: Microparticles and Protein Complexes E45mentioning

confidence: 63%

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

György

Módos

Pállinger

et al. 2011

Blood

380

410

View full text Add to dashboard Cite

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“…Although many human studies have been published correlating AA and IC to oxidation-specifi c epitopes to anatomic coronary and carotid and peripheral arterial disease ( 8,14 ), the focus of the current analysis was CAD risk prediction. Relatively few studies have evaluated their prognostic value in predicting CAD events and the results have been inconsistent ( 6,10,12,13,32,33 ). Initial studies have shown predictive value ( 10,12,13,33 ), but more recent studies with appropriate size and multivariable adjustment have shown no independent predictive value ( 6,32,34 ).…”

Section: Discussionmentioning

confidence: 99%

“…Relatively few studies have evaluated their prognostic value in predicting CAD events and the results have been inconsistent ( 6,10,12,13,32,33 ). Initial studies have shown predictive value ( 10,12,13,33 ), but more recent studies with appropriate size and multivariable adjustment have shown no independent predictive value ( 6,32,34 ). Some of the reasons for these disparate fi ndings may be the lack of power, different methodologies for AA and IC measurement, measurement of either IgG of IgM but not both classes, and heterogeneous patient cohorts.…”

Section: Discussionmentioning

confidence: 99%

Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

Ravandi

Boekholdt

Mallat

et al. 2011

Journal of Lipid Research

118

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“…(24) and involvement of C3 and C5 in endothelium activation and leukocyte recruitment to inflammatory sites have been demonstrated. CICs are known to increase with age and play an important role in the induction of vascular damage, leading to low-grade chronic inflammation of the vascular wall (25). Because C3 is the central molecule in the complement system, the level of C3 was measured in this study and its concentration was found to be the highest in the subjects with LDLcholesterolՆ160 mg/dL.…”

Section: Discussionmentioning

confidence: 94%

Immune and Nutrition Status in Elderly Koreans with HyperLDL-Cholesterolemia

Lee¹,

Park

Nam

et al. 2006

J Nutr Sci Vitaminol

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Summary Although the effects of nutrition and immune status on disease development have been investigated, little attention has been given to changes in immune function in the elderly vulnerable to coronary artery disease (CAD). Our objective was to evaluate the association between immune variables and CAD risk factors, and nutritional factors related to immune and lipid profiles in elderly Koreans ( n ϭ 90). The subjects were divided into three groups based on serum low-density lipoprotein cholesterol (LDL-cholesterol) level: risk ( Ն 160 mg/dL), borderline (130-160 mg/dL), and control groups ( Ͻ 130 mg/dL). Concanavalin A-induced lymphocyte proliferation rate and interleukin (IL)-2 secretion were significantly lower in the risk group than the control group. The subjects in the risk group showed the highest serum concentrations of proinflammatory mediators such as complement 3 (C3), IL-1 ␤ , and IL-1 receptor antagonist (IL-1RA). The nutrient intake status of the subjects was generally satisfactory without differences among groups. IL-1RA concentration was negatively associated with intake of vitamin E and C3 was positively related to intake of Ca and Fe in the subjects with LDL-cholesterol Ն 130 mg/dL. This study suggests that elderly individuals with high serum LDL-cholesterol are in a mild chronic inflammation state and micronutrient status such as vitamin E, Ca, and Fe may relate to this state. Key Words immune function, nutritional factor, elderly, T-lymphocytes, cytokines Coronary artery disease (CAD) is a leading cause of death in elderly Koreans ( 1 ). Lipid metabolism and inflammatory responses are now recognized as factors playing a central role in the pathogenesis of CAD. In particular, LDL particles trapped in an intima undergo progressive oxidation and are internalized by macrophages and become foam cells, resulting in the formation of fatty streaks and fibrous plaque. These lesions are advanced and activated by growth factors and cytokines secreted from endothelial cells, smooth muscle cells, macrophages, and platelets ( 2-4 ).Cytokines are regulators of host responses to infection, inflammation, and trauma. The production and activity of the cytokines are tightly controlled. The main pro-inflammatory cytokines, such as interleukin (IL)-1 ␤ , IL-6, and tumor necrosis factor (TNF), are increased in the process of CAD. Inflammatory cytokines themselves were shown to be major inducers of their own soluble receptors/antagonist upregulation ( 5 ). For example, IL-1 receptor antagonist (IL-1RA), a protein with high homology with IL-1 but without IL-1 activity ( 6 ), was induced by inflammatory mediators. Serum levels of soluble cytokine receptors were reported to correlate with disease activity in a variety of clinical situations.Nutrition is an important factor affecting the cytokine level and inflammation response. Since diet is modifiable, nutrition could play a role in controlling CAD. It is of interest to evaluate the inflammatory response in elderly subjects with risk factors for CAD. In this stud...

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Circulating Immune Complexes in 50-Year-Old Men as a Strong and Independent Risk Factor for Myocardial Infarction

Abstract: This prospective study shows that CICs alone or in combination with autoantibodies against cardiolipin in healthy males at 50 years of age predict subsequent MI between the age of and 70 years.

Cited by 57 publications

References 39 publications

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

Immune and Nutrition Status in Elderly Koreans with HyperLDL-Cholesterolemia

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