Innate and acquired immunity in atherogenesis

Department of Medicine, University of California San Diego, La Jolla, California, USA.
Nature Medicine (Impact Factor: 27.36). 12/2002; 8(11):1218-26. DOI: 10.1038/nm1102-1218
Source: PubMed


Traditional risk factors like hypercholesterolemia are important for atherogenesis, but it is now apparent that the immune system also plays an important role. Uncovering the mechanism by which specific components of the immune system impact atherogenesis will not only provide new insights into the pathogenesis of lesion formation but could also lead to novel therapeutic approaches that involve immune modulation.

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Available from: Christoph J Binder, Jul 15, 2014
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    • "Thirty-one patients and twelve healthy controls participated in this study with a 4-month follow up. Development of atherosclerosis was affected by the adaptive immune system (Binder et al., 2002) and Th1 are an important class of immune cells in the pathogenesis of atherosclerosis. Expression of vascular cell-adhesion molecule 1 (VCAM1) on endothelium in response to bioactive lipids such as ox-LDL that have been trapped within the arterial wall, is an early sign of the immune response to begin the process of atherosclerosis (Cybulsky & Gimbrone, 1991; Dai et al., 2004; Nakashima et al., 1998). "
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    ABSTRACT: Background: The aim of present study is evaluation of vitamin A supplementation efficacy on IFN-ɣ and T-bet gene expression in atherosclerotic patients. Methods: Thirty-one patients and 15 healthy controls participated in this study. Healthy control and patients in Vitamin A group received 25 000 IU retinyl palmitate daily for 4 months. Control patients also received 1 pearl of placebo per day up to 4 months. Gene expression levels were assessed by real-time PCR using SYBR green detection method. Results: IFN-γ gene expression in fresh cells of patients taking vitamin A declined slightly (0.85-fold, p = 0.068), whereas the expression of this gene was increased in patients taking placebo, and in healthy control subjects 1.2-fold (p = 0.267) and 1.7-fold (p = 0.580), respectively. There were no significant difference (p = 0.159) between 3 groups in terms of IFN-γ gene expression in cells stimulated with PHA. In order to determine whether PHA stimulation of PBMCs in vitro had an effect on T-bet expression, we measured the difference between the 3 groups of studied. The results showed significant differences between the groups (p = 0.046). IFN-γ gene expression in cells activated with ox-LDL in healthy control subjects and patients taking vitamin A, was reduced 0.43 (p = 0.0001) and 0.41 (p = 0.001) respectively, but in placebo patients was increased 2.2-fold (p = 0.959). Conclusion: Considering role of vitamin A on suppression of Th1 cells in atherosclerotic patients, it can be concluded that vitamin A supplementation may be advantageous for these patients.
    Immunological investigations 12/2014; 44(2). DOI:10.3109/08820139.2014.953635 · 1.99 Impact Factor
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    • "Accumulation of oxidized lipids in the vasculature is known to trigger an immune response that leads to the formation of acquired antibodies against these oxidized lipids [12,13,15-17,20]. The plasma titers of these acquired oxidized lipid reactive antibodies correlate with the risk of clinical manifestations of atherosclerosis, although depending on the method used in the measurements, the correlation can be positive or negative [20,22-24,29,30]. "
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    ABSTRACT: Rupture of a saccular intracranial aneurysm (sIA) causes an often fatal subarachnoid hemorrhage (SAH). Why some sIAs rupture remains unknown. Since sIA walls bear some histological similarities with early atherosclerotic lesions, we hypothesized that accumulation and oxidation of lipids might occur in the sIA wall and might associate with sIA wall degeneration. Tissue samples from sIA fundi (n = 54) were studied with histochemistry and a panel of previously characterized antibodies for epitopes of oxidized LDL (OxLDL). Plasma samples from sIA carriers (n = 125) were studied with ELISA and EIA for IgG and IgM -antibodies against a panel of OxLDL epitopes. Lipid accumulation, foam cells, and oxidized lipids were found both in unruptured and ruptured sIA walls. Lipid accumulation associated with wall degeneration (P < 0.001), as did the expression of adipophilin, a marker of lipid ingestion by cells. Lipid accumulation associated also with loss of mural cells (P < 0.001), as did the accumulation of OxLDL (P < 0.001). Plasma IgG antibody titers against OxLDL or malondialdehyde modified LDL were higher in patients with unruptured sIAs than in patients with aneurysmal SAH (P ≤ 0.001). A trend but not statistically significant differences were found in plasma IgM antibodies against oxidized lipids. Accumulation of lipids and their oxidation in the sIA wall associates with the degeneration of the sIA wall. Acquired immunity against oxidized lipid epitopes may be protective of lipid associated sIA wall degeneration, but warrants further studies.
    10/2013; 1(1):71. DOI:10.1186/2051-5960-1-71
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    • "Furthermore, accelerated generation and vascular deposition of AGEs in addition to AGE interactions with RAGE in diabetes initiate oxidative reactions that promote the formation of oxidized LDL (oxLDL) (Basta et al., 2004). Oxidation of LDL within the sub-endothelial space (intima) enhances the pro-inflammatory properties of the endothelium (Mazière and Mazière, 2009) and activates both innate and adaptive arms of the immune system (Binder et al., 2002; Hansson et al., 2002). "
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    ABSTRACT: A central mechanism driving vascular disease in diabetes is immune cell-mediated inflammation. In diabetes, enhanced oxidation and glycation of macromolecules, such as lipoproteins, insults the endothelium, and activates both innate and adaptive arms of the immune system by generating new antigens for presentation to adaptive immune cells. Chronic inflammation of the endothelium in diabetes leads to continuous infiltration and accumulation of leukocytes at sites of endothelial cell injury. We will describe the central role of the macrophage as a source of signaling molecules and damaging by-products which activate infiltrating lymphocytes in the tissue and contribute to the pro-oxidant and pro-inflammatory microenvironment. An important aspect to be considered is the diabetes-associated defects in the immune system, such as fewer or dysfunctional athero-protective leukocyte subsets in the diabetic lesion compared to non-diabetic lesions. This review will discuss the key pro-inflammatory signaling pathways responsible for leukocyte recruitment and activation in the injured vessel, with particular focus on pro- and anti-inflammatory pathways aberrantly activated or repressed in diabetes. We aim to describe the interaction between advanced glycation end products and their principle receptor RAGE, angiotensin II, and the Ang II type 1 receptor, in addition to reactive oxygen species (ROS) production by NADPH-oxidase enzymes that are relevant to vascular and immune cell function in the context of diabetic vasculopathy. Furthermore, we will touch on recent advances in epigenetic medicine that have revealed high glucose-mediated changes in the transcription of genes with known pro-inflammatory downstream targets. Finally, novel anti-atherosclerosis strategies that target the vascular immune interface will be explored; such as vaccination against modified low-density lipoprotein and pharmacological inhibition of ROS-producing enzymes.
    Frontiers in Endocrinology 06/2013; 4:68. DOI:10.3389/fendo.2013.00068
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