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.
Field of science
- /medical and health sciences/basic medicine/immunology/autoimmune diseases
- /medical and health sciences/health sciences/inflammatory diseases
- /medical and health sciences/clinical medicine/cardiology/cardiovascular diseases/arteriosclerosis
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