Abstract
Atherosclerosis is a long-term, chronic inflammatory disease of the vessel wall leading to the formation of occlusive or rupture-prone lesions in large arteries. Complications of atherosclerosis can become severe and lead to cardiovascular diseases (CVD) with lethal consequences. During the last three decades, chemokines and their receptors earned great attention in the research of atherosclerosis as they play a key role in development and progression of atherosclerotic lesions. They orchestrate activation, recruitment, and infiltration of immune cells and subsequent phenotypic changes, e.g., increased uptake of oxidized low-density lipoprotein (oxLDL) by macrophages, promoting the development of foam cells, a key feature developing plaques. In addition, chemokines and their receptors maintain homing of adaptive immune cells but also drive pro-atherosclerotic leukocyte responses. Recently, specific targeting, e.g., by applying cell specific knock out models have shed new light on their functions in chronic vascular inflammation. This article reviews recent findings on the role of immunomodulatory chemokines in the development of atherosclerosis and their potential for targeting.
Highlights
Chemokines are a large class of secreted cytokines with the capability of inducing cellular migration by forming chemoattractant gradients, a process known as chemotaxis [1]
After aiding the homing of these cells to the lesions, chemokines like CXCL8 activate the endothelial barrier by increasing adhesion molecules to allow the infiltration of various immune cells
Chemokines like CXCL16 directly act as adhesion molecules to the CXCR6 expressed on platelets
Summary
Chemokines are a large class of secreted cytokines with the capability of inducing cellular migration by forming chemoattractant gradients, a process known as chemotaxis [1]. Invasion of the arterial wall by leukocytes is one of the key drivers of atherosclerotic lesion development and it involves several stages, such as recruitment, adhesion and trans-endothelial infiltration of the cells These processes are aided by a variety of chemokines, like CXCL1 and CCL2. Vascular injury induced or diet-induced atherosclerotic mouse models, such as apolipoprotein-E deficient (ApoE−/−) or low-density lipoprotein receptor deficient (Ldlr−/−) mice on Western type diets are applied These mice are genetically modified resulting in lack of certain chemokines or chemokine receptors (systemically or in a cell-specific manner) in order to investigate the role of the target molecules in the context of the atherosclerosis. Fituhrtahsebremeonrseh, aocwtinvathteadt cmhaecmroopkhinaegersecseecprteotrescihnefmluoeknicneesenthdaottshteimliaullapteertmhiesalbeiuliktyo,cywtehircehcruisitmanenimt pproorcteasnstanasdpietcht afsobreleenukshoocywtne tthraant scmheimgroaktiionne (rCecrepateodrswinitflhuBeinocrenednedro.ctohmel)i.al permeability, which is an important aspect for leukocyte transmigration (Created with Biorender.com)
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