ATHEROMOTO · Vascular inflammation and atherosclerosis
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2009-09-01 → 2011-08-31
- Финансиране от ЕС
- 239 551 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Връзката между автоимунните процеси и развитието на атеросклероза се анализира чрез създаден модел с мишки. Това помага да се разбере как високите нива на мазнини в кръвта засилват възпаленията и ускоряват запушването на кръвоносните съдове.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Vascular inflammation and atherosclerosis
Project context Patients with aggressive inflammatory diseases, including autoimmune diseases, exhibit a higher incidence of atherosclerosis, suggesting that autoimmune processes may play a role in atherosclerosis progression. Despite awareness of this inflammatory nature of atherosclerosis, the causes of the inflammation and the exact nature of the putative antigens that elicit the immune reaction are not well characterised. One reason for this deficit is the lack of an appropriate animal model. Project objectives Our objectives were to create a mouse model combining autoimmunity and atherosclerosis and to investigate how hyperlipidemia affects autoimmune reactions and atherogenesis in this mouse model. Project outcomes We established a mouse model combining autoimmunity and hyperlipidemia by creating leukocyte deficiency in type IIB Fc Receptor (FcRIIB) in LDL receptor knockout background using bone marrow transplantation. We evaluated atherosclerosis progression in mice under two experimental settings; moderate and aggressive hyperlipidemia. Under aggressive Western diet conditions (plasma cholesterol levels around 800 mg/dl), and in the absence of FcRIIB, the mouse model was characterised by high levels of circulating immune complexes, immunoglobulin G and anti-nuclear antibodies, which are common in a typical autoimmune disease. In addition to impaired renal function and splenomegaly, the progression of atherosclerosis was more aggressive in these autoimmune mice. However, under moderate lipidemic conditions (plasma cholesterol levels around 400 mg/dl), levels of autoimmune markers were lower and the extent of atherosclerosis was similar with or without FgRIIB expression. Using proteomic approaches, we discovered many molecular targets for these autoimmune reactions within the atherosclerotic plaques. We have concluded that autoimmunity accelerates atherogenesis, and hyperlipidemic conditions exasperate autoimmune responses leading to autoimmunity-driven atherosclerosis. Our results suggest that treatment of cardiovascular cases by lipid-lowering medication may slow down the inflammatory insult and protect against the progression of cardiovascular disease.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Atherosclerosis is an immunoinflammatory disease of the arterial wall that carries an important socio-economic burden. Atherosclerotic lesions contain activated T cells and specific cytokines along with immunoglobulins. Several studies have shown that atherosclerotic patients develop a perturbed inflammation toward arterial proteins suggesting that autoimmune processes may play a role in atherosclerosis progression. Moreover, patients with aggressive inflammatory diseases such as autoimmune diseases, including SLE, rheumatoid arthritis and type I diabetes, exhibit a higher incidence of atherosclerosis and are at significant risk of premature cardiovascular disease. The continued emergence of cardiovascular diseases and accelerated atherosclerosis in a wide variety of autoantibody-driven diseases emphasizes the need to identify early diagnostic markers and immunotherapeutic targets for the treatment of these complications. The specific hypothesis is that the initiation and progression of atherosclerosis is regulated by autoantibodies directed toward vascular wall components, defects in immune complex (IC) and autoantibody clearance. Our long term goal is to understand the cellular and humoral immunity/autoimmunity basis of atherosclerosis. We will focus our study on analyzing the inhibitory Fc type IIB receptor of immunoglobulin G (FcgRIIB) for the creation of the mouse line of autoimmunity. FcgRIIB is critical in controlling excessive antibody production by B lymphocytes, regulating macrophage reactivity and controlling autoimmunity. We propose to modulate the expression of this “suppressor” of autoimmunity in a hyperlipidemic mouse background. Our specific aims are: Aim I- To create a mouse model that combines of autoimmunity and hypercholesterolemia by silencing the FcgRIIB gene expression in LDLR-/- mouse background. Aim II- To identify panels of antigens that elicit an autoimmune response in this mouse model using a proteomic approach.
Оригинален текст от CORDIS (на английски).
Участници
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция
Връзки
Данни: CORDIS, © Европейски съюз