Dataset Information

Inflammatory Chemokines in Atherosclerosis.

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.

SUBMITTER: Gencer S

PROVIDER: S-EPMC7911854 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Inflammatory Chemokines in Atherosclerosis.

Gencer Selin S Evans Bryce R BR van der Vorst Emiel P C EPC Döring Yvonne Y Weber Christian C

Cells 20210125 2

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 ...[more]

PMID: 33503867

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Project description:The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis, i.e., stroke and myocardial infarction are definable but not the plaque burden. Platelet indices including platelet count and mean platelet volume (MPV) and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities, e.g., altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1bα, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation and atherosclerosis.

Project description:BackgroundAtherosclerosis begins in childhood with the occurrence of inflammatory vascular wall alterations that are detectable with B-mode ultrasound. Chemokines appear to be involved in the development of these alterations given that they occur early in the atherosclerotic pathway as mediators of vascular inflammation. However, this has not extensively been investigated. Therefore, we studied in healthy young children whether chemokines monocyte chemotactic protein 1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and vascular and intercellular adhesion molecules (VCAM and ICAM) related to vascular characteristics of the carotid artery.Methods and resultsWe obtained demography, anthropometry, and overnight fasting plasma of 139 eight-year-old children of the Wheezing Illnesses Study Leidsche Rijn birth cohort. Carotid intima-media thickness (CIMT), distensibility, and Young's Elastic Modulus (YEM) of the common carotid artery were measured sonographically. Chemokine plasma levels were assessed using a multiplex assay. We studied the relation between the chemokines and vascular characteristics using multivariable linear regression analyses with adjustments for sex, systolic blood pressure, homeostasis model assessment of insulin resistance, triglycerides, low-density lipoprotein- and high-density lipoprotein-cholesterol. Of the studied chemokines, RANTES related to common carotid distensibility and YEM. One standard deviation increase in RANTES level related to a 5.45-MPA(-1) (95% confidence interval [CI], -9.43, -1.39; P=0.01) decrease in distensibility and to a 5.55-kPa increase in YEM (95% CI, 0.40, 10.85; P=0.03). RANTES did not relate to CIMT. MCP-1, VCAM, and ICAM did not relate to any of the studied vascular characteristics.ConclusionRANTES appears to be involved in the development of preatherosclerotic inflammatory vascular alterations already in healthy, young children. This may provide further insight into the early-life origins of atherosclerosis.

Dataset Information

Inflammatory Chemokines in Atherosclerosis.

Publications

Inflammatory Chemokines in Atherosclerosis.

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