Targeting B Cells in Atherosclerosis

Abstract

Atherosclerosis is a multifactorial disease with multiple genetic and environmental risk factors and is characterized by the formation of a plaque in the artery wall. Plaque formation is initiated on trapping of low-density lipoproteins (LDL) in the intima where they undergo oxidation and acquire immunogenic properties. The oxidation of LDL results in the generation of many different immunogenic epitopes, termed oxidation-specific epitopes (OSEs), that are recognized by both innate and adaptive immune mechanisms. Monocytes that enter the intima differentiate to macrophages and take up oxidized LDL (oxLDL), which leads to their activation and results in the formation of foam cells. During this process, macrophages are stimulated by lipid-derived danger-associated molecular patterns such as oxidized phospholipids that promote cytokine secretion via scavenger receptor CD36 and Toll-like receptor signaling and cholesterol crystals, which activate the inflammasome followed by interleukin-1β production.1,2 Plaque inflammation is further amplified and sustained as a result of recruitment/activation of the adaptive immune system and is an important and potentially central driving force in promoting vulnerable plaque features. Plaque rupture results in life-threatening manifestations, such as myocardial infarction and stroke. Surgery and reducing the risk of clotting are powerful end-stage solutions and lipid lowering is an effective preemptive treatment. However, significant risk remains and new strategies to target underlying causes of vulnerable plaque development and rupture are important future goals. Although an adaptive immune system is not essential for atherosclerosis to develop, 4,5 many studies now demonstrate that it has a diverse range of important site-specific influences on plaque development and inflammation. (Auto)immune reactivity to a range of autoantigens, but most prominently modified LDL, is a mark of human cardiovascular disease and in experimental models plays a significant role in promoting atherosclerotic plaque progression. Atherosclerosis is a distinct case compared with typical autoimmune diseases because (1) the major autoantigen oxLDL is really a modified self-antigen or neo-self-antigen and (2) the oxLDL autoantigen, rather than playing a physiological function, is pathogenic and disease causing. There are also other autoantigens involved, such as heat shock protein 60, 6,7 and the impact of other autoimmune diseases in promoting atherosclerosis such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is well known. 8,9 The role of T cells and interferon-γ-secreting Th1 cells, in particular, as key drivers of plaque inflammation is well documented, and experimental approaches to dampen these responses by enhancing the activity of regulatory T cells are being tested. More recently, it was found that B cells could Targeting B Cells in Atherosclerosis Closing the Gap From Bench to BedsideDimitrios Tsiantoulas, Andrew P. Sage, Ziad Mallat, Christoph J. BinderAbstract-Atheroscl...

X-Box Binding Protein-1 Dependent Plasma Cell Responses Limit the Development of Atherosclerosis

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Belimumab in systemic lupus erythematosus: a perspective review

“…Currently, studies are underway to determine if belimumab would be an effective treatment for other diseases, including Sjogren's syndrome and atherosclerosis [De Vita et al 2014;Tsiantoulas et al 2015].…”

Associação entre inflamação do tecido adiposo epicárdico e doença arterial coronariana: um estudo clinicopatológico

“…A aterosclerose é uma doença progressiva 12,13 , caracterizada pelo espessamento assimétrico da camada íntima da artéria 14 . Recentemente foi descrito que a camada média e adventícia também são afetadas 15 .…”

“…É uma doença multifatorial com envolvimento de muitos fatores de risco 13 , sendo os principais modificáveis o tabagismo, hipertensão arterial sistêmica, hiperlipidemia, diabetes mellitus, doença renal, e adiposidade 16 . Apresenta também componente genético 13 .…”

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