Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in Apoe−/− mice

Hjerpe, Charlotta; Johansson, Daniel K.; Hermansson, Andreas; Hansson, Göran; Zhou, Xinghua

doi:10.1016/j.atherosclerosis.2009.10.003

Cited by 55 publications

(42 citation statements)

References 16 publications

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“…In contrast, DCs loaded with malondialdehyde-modified LDL aggravated atherosclerosis in Apoe −/− mice. 167 Similarly, increased lesion development was found when Apoe −/− mice expressing β-galactosidase under the transcriptional regulation of the SM22α promoter received bone marrow-derived DCs loaded with β-galactosidase-specific peptides. 168 The above DC immunization approaches have several limitations.…”

Section: Therapeutics For Atherosclerosismentioning

confidence: 99%

Macrophages and Dendritic Cells

Cybulsky

Cheong

Robbins

2016

Circulation Research

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Atherosclerosis is a complex chronic disease. The accumulation of myeloid cells in the arterial intima, including macrophages and dendritic cells (DCs), is a feature of early stages of disease. For decades, it has been known that monocyte recruitment to the intima contributes to the burden of lesion macrophages. Yet, this paradigm may require reevaluation in light of recent advances in understanding of tissue macrophage ontogeny, their capacity for self-renewal, as well as observations that macrophages proliferate throughout atherogenesis and that self-renewal is critical for maintenance of macrophages in advanced lesions. The rate of atherosclerotic lesion formation is profoundly influenced by innate and adaptive immunity, which can be regulated locally within atherosclerotic lesions, as well as in secondary lymphoid organs, the bone marrow and the blood. DCs are important modulators of immunity. Advances in the past decade have cemented our understanding of DC subsets, functions, hematopoietic origin, gene expression patterns, transcription factors critical for differentiation, and provided new tools for study of DC biology. The functions of macrophages and DCs overlap to some extent, thus it is important to reassess the contributions of each of these myeloid cells taking into account strict criteria of cell identification, ontogeny, and determine whether their key roles are within atherosclerotic lesions or secondary lymphoid organs. This review will highlight key aspect of macrophage and DC biology, summarize how these cells participate in different stages of atherogenesis and comment on complexities, controversies, and gaps in knowledge in the field. (Circ Res. 2016;118:637-652.

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Section: Therapeutics For Atherosclerosismentioning

confidence: 99%

Macrophages and Dendritic Cells

Cybulsky

Cheong

Robbins

2016

Circulation Research

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“…Perhaps too, resolving which DC subsets are most affected, which coreceptors are expressed, and their interaction with various T-cells including Treg, may help explain another study which reported a decrease in atherosclerosis from adoptive transfer of mature DCs pulsed with oxLDL (688). Yet, in another study, there was an increase in atherosclerosis with transfer of DC treated with MDA-LDL (769). Both studies used DCs expanded from bone marrow by incubation with GM-CSF.…”

Section: Dcs As Complex Modulators Of Atherogenesismentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

389

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…[39] reported that dendritic cells that have been isolated, pulsed with MDA-LDL in presence of the TLR4 activator LPS and subsequently transferred into apo E -/-mice aggravate atherosclerosis.…”

Section: Targeting Cellular and Humoral Immune Responses Against Apo mentioning

confidence: 99%

Apolipoprotein B100 autoimmunity and atherosclerosis – disease mechanisms and therapeutic potential

Nilsson

Björkbacka

Fredrikson

2012

Current Opinion in Lipidology

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Purpose of reviewAdaptive immune responses have been shown to play an important role in the atherosclerotic disease process and both pathogenic and protective immunity has been identified. Apolipoprotein (apo) B100 appears to be a key antigen and novel therapies modulating immune responses against apo B100 have shown promising results in experimental models. This review will discuss recent developments in the mechanistic understanding of apo B100 autoimmunity and approaches taken to use this knowledge for development of novel therapies. Recent findingsIt has recently been shown that not only apo B100 modified by oxidation but also nonmodified apo B100 is targeted by autoimmune responses. This implies that a corresponding set of regulatory T cells with the same antigen specificity must exist and that these cells under normal circumstances are able to prevent autoimmunity against LDL. Recent studies also suggest that the athero-protective effect of apo B100 peptide immunization acts by reenforcing the activity of such cells. SummaryThese novel findings suggest that aggravation of plaque inflammation may occur as result of a local loss of tolerance against LDL in the plaque due to insufficient activity of regulatory T cells. Restoration of lost tolerance represents an interesting novel approach for treatment of cardiovascular disease.

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Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in Apoe−/− mice

Cited by 55 publications

References 16 publications

Macrophages and Dendritic Cells

Macrophages and Dendritic Cells

Molecular Biology of Atherosclerosis

Apolipoprotein B100 autoimmunity and atherosclerosis – disease mechanisms and therapeutic potential

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