Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Dunér, Pontus; To, Fong; Berg, Katarina; Alm, Ragnar; Björkbacka, Harry; Engelbertsen, Daniel; Fredrikson, Gunilla Nordin; Nilsson, Jan; Bengtsson, Eva

doi:10.1016/j.atherosclerosis.2010.07.014

Cited by 23 publications

(21 citation statements)

References 31 publications

(20 reference statements)

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“…Indeed, by screening human plasma we found both IgM and IgG binding to several MDA-modified extracellular matrix proteins including collagen type I, collagen type III, fibronectin, and the basement membrane protein laminin. 7,8 We also showed that MDA can leak out of the LDL-particle and modify extracellular matrix proteins in vitro. 7 In addition, by using in-house produced antibodies recognizing different MDA-modified proteins, we have identified both MDA-modified fibronectin and MDA-modified laminin in atherosclerotic lesions.…”

Section: Introductionmentioning

confidence: 80%

“…Since LDL-aggregation in the development of atherosclerotic lesions occurs by binding to subendothelial matrix proteoglycans, we asked whether LDL-oxidation would result in MDA-modifications of proteins present in the closely situated basement membrane. In addition, the identification of auto-antibodies against the MDA-modified basement membrane protein laminin 8 implied presence of MDA-modified basement membrane components. Thus we stained cross-sections of human carotid lesions with an antibody recognizing MDA-modified collagen type IV produced in hen, a pre-immunization control IgY, anti-collagen type IV, anti-CD68 recognizing macrophages and oil red O staining lipids.…”

Section: Mda-collagen Type IV Is Present Adjacent To Endothelial Cellmentioning

confidence: 99%

“…7,8 To test whether antibodies against MDA-modified collagen type IV were associated to the amount of MDA-modified collagen type IV in the lesions, we measured the amount of IgM and IgG against MDA-modified collagen type IV in plasma from the same patients from whom the carotid lesions were removed. Indeed, both IgM and IgG were positively associated with the amount of MDA-modified collagen type IV, but not with native collagen type IV (Supplementary table 2).…”

Section: Plasma Igm and Igg Against Mda-collagen Type IV Are Associatmentioning

confidence: 99%

“…7 In addition, by using in-house produced antibodies recognizing different MDA-modified proteins, we have identified both MDA-modified fibronectin and MDA-modified laminin in atherosclerotic lesions. 7,8 Although previous studies identified antibodies against different modified matrix proteins, the protein levels in atherosclerotic lesions and their relation to plaque stability and 5 cardiovascular events have not been investigated. Modification of basement membrane components due to nearby lipid oxidation may result in decreased endothelial cell attachment, which will promote cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

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Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

et al. 2015

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Increased aldehyde-modification of collagen type IV in symptomatic plaques -A possible cause of endothelial dysfunction.Dunér, Pontus; Goncalves, Isabel; Grufman, Helena; Edsfeldt, Andreas; To, Fong; Nitulescu, Mihaela; Nilsson, Jan; Bengtsson, Eva Link to publication Citation for published version (APA): Dunér, P., Goncalves, I., Grufman, H., Edsfeldt, A., To, F., Nitulescu, M., ... Bengtsson, E. (2015). Increased aldehyde-modification of collagen type IV in symptomatic plaques -A possible cause of endothelial dysfunction. Atherosclerosis, 240(1), 26-32. DOI: 10.101626-32. DOI: 10. /j.atherosclerosis.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Abstract ObjectiveSubendothelial LDL-adhesion and its subsequent oxidation are considered as key events in the development of atherosclerotic lesions. During oxidation of LDL, reactive aldehydes such as malondialdehyde (MDA) are formed, which modify apolipoproteinB100. However, the possibility that these reactive aldehydes could leak out of the LDL-particle and modify surrounding extracellular matrix proteins has been largely unexplored. We have investigated if aldehyde-modification of collagen type IV, one of the major basement membrane components, in plaques is associated with cardiovascular events. MethodsThe amount of MDA-modified collagen type IV and native collagen type IV were determined in homogenates from 155 carotid artery lesions, removed by endarterectomy from patients with or without previous cerebrovascular events. ResultsPlaque MDA-collagen type IV, but not native collagen type IV, correlated with oxidized LDL (r=0.31, P<0.001) and lipoprotein-associated phospholipase A2 (r=0.44, P<0.001).MDA-collagen type IV was increased in lesions from symptomatic patients compared to lesions from asymptomatic patients. Autoantibodies against MDA-collagen type IV in plasma correlated with the amount of MDA-collagen type IV in lesions. MDA-modification of collagen type IV decreased endothelial cell attachment. In addition, culture of endothelial cells with MDA-modified collagen type IV increased vascular cell adhesion molecule expression and reduced the anti-coagulant proteins thrombomodulin and endothelial protein C receptor. In the lesions native collagen type IV, but not MDA-collagen type IV, was positively associated with thrombomodulin. Conclusion 3The present observations imply that aldehyde-modification of collagen type IV, associated with LDL oxidation, in atherosclerotic plaques may cause endothelial d...

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Section: Introductionmentioning

confidence: 80%

Section: Mda-collagen Type IV Is Present Adjacent To Endothelial Cellmentioning

confidence: 99%

Section: Plasma Igm and Igg Against Mda-collagen Type IV Are Associatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

et al. 2015

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“…Indeed, we have identified autoantibodies against several aldehyde-modified matrix proteins, including MDA-modified laminin present in basement membranes. Interestingly, these autoantibodies were associated with less cardiovascular disease in a prospective cohort, which may imply a protective effect in humans [22].…”

Section: Introductionmentioning

confidence: 90%

Autoantibodies against basement membrane collagen type IV are associated with myocardial infarction

McLeod

Dunér

Samnegård

et al. 2015

IJC Heart & Vasculature

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BackgroundCollagen type IV is the major constituent of basement membranes underlying endothelial cells and is important for endothelial cell attachment and function. Autoantibodies against native collagen type IV have been found in various autoimmune diseases. Oxidation of LDL in the vascular wall results in the formation of reactive aldehydes, which could modify surrounding matrix proteins. Like oxidized LDL, these modified matrix proteins are likely to induce immune responses. We examined whether autoantibodies against native or aldehyde-modified collagen type IV are associated with myocardial infarction.MethodsIgM and IgG against native and aldehyde-modified collagen type IV were measured by ELISA in serum from 387 survivors of a first myocardial infarction and 387 age- and sex-matched controls.ResultsPost-infarction patients had significantly increased levels of IgM against native collagen type IV, and IgG against native collagen type IV was present at detectable level in 17% of patients as opposed to 7% of controls (p < 0.001). Controlling for major cardiovascular risk factors demonstrated that the presence of IgG against native collagen type IV was associated with myocardial infarction (OR 2.9 (1.6–5.4), p = 0.001). Similarly, subjects in the highest quartile of IgM against native collagen type IV had increased risk of having suffered myocardial infarction (OR 3.11 (1.8–5.4), p < 0.001) after adjusting for cardiovascular risk factors. In contrast, IgG against aldehyde-modified collagen type IV was decreased in myocardial infarction patients, but this association was not independent of established cardiovascular risk factors.ConclusionAutoantibodies against collagen type IV are associated with myocardial infarction independently of traditional cardiovascular risk factors.

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ONOO⁻‐mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells

Liang

Liu

Zheng

et al. 2022

Cell Biology International

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Atherosclerosis (AS) is a principal contributor to stroke and coronary heart disease in humans characterized by chronic low-grade inflammation. The extracellular matrix (ECM) plays critical roles in regulating the function of arteries. However, the effect of changes in ECM on AS development is rarely studied. In this context, we intend to study the effect of oxidizing agent peroxynitrite (ONOO − )-mediated oxidization of ECM proteins on the biological behaviors of vascular smooth muscle cells (SMCs) and the development of AS. AS mouse models were established, and mouse coronary artery smooth muscle cells (MCASMCs) were cultured in vitro to derive ECM (SMC-ECM), which was obtained by deoxycholate (DOC)-based decellularization. Further, MCASMCs were subjected to the determination of ECM oxidative damage and ECM protein structure. Finally, roles of ONOO − -mediated oxidization of ECM in SMC adhesion and migration and in AS development were explored through Transwell assay, transcriptome sequencing, and gene enrichment analysis. High concentration of ONOO − was found in the serum of AS mice, and ONOO − could stimulate the development of AS. SMC-ECM with intact structure can be obtained in vitro by DOC treatment. Functionally, ONOO − -mediated oxidization destroyed the three-dimensional structure of SMC-ECM proteins, affected SMC adhesion and migration and promoted the absorption efficiency of lipids while reducing the efflux of cholesterol. In addition, the expression of inflammation-and oxidative stressrelated genes was significantly increased in ECM subjected to ONOO − -mediated oxidization, thereby contributing to AS progression. ONOO − -mediated oxidative modification of ECM aggravates AS by affecting the biological behavior of SMCs.

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Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Abstract: "Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe (-/-) AbstractBackground: LDL oxidation in the vascular wall is associated with aldehyde

Cited by 23 publications

References 31 publications

Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

Autoantibodies against basement membrane collagen type IV are associated with myocardial infarction

ONOO⁻‐mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells

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Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Abstract: "Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe (-/-) AbstractBackground: LDL oxidation in the vascular wall is associated with aldehyde

Cited by 23 publications

References 31 publications

Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

Autoantibodies against basement membrane collagen type IV are associated with myocardial infarction

ONOO−‐mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells

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ONOO⁻‐mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells