Regulation of Atherogenesis by Chemokines and Chemokine Receptors
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Atherosclerosis is a chronic inflammatory and metabolic disorder affecting large- and medium-sized arteries, and the leading cause of mortality worldwide. The pathogenesis of atherosclerosis involves accumulation of lipids and leukocytes in the intima of blood vessel walls creating plaque. How leukocytes accumulate in plaque remains poorly understood; however, chemokines acting at specific G protein-coupled receptors appear to be important. Studies using knockout mice suggest that chemokine receptor signaling may either promote or inhibit atherogenesis, depending on the receptor. These proof of concept studies have spurred efforts to develop drugs targeting the chemokine system in atherosclerosis, and several have shown beneficial effects in animal models. This study will review key discoveries in basic and translational research in this area.
KeywordsAtherosclerosis Cardiology Immunology Inflammation Antagonist
This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (Bethesda, MD, USA).
Conflict of interest
Note added in proof
We have recently reported that Ccr7-deficient ApoE knockout mice fed a Western diet have markedly increased atherosclerotic plaque. This effect was due to Ccr7 expression on a bone marrow-derived cell and was associated with increased lesional and blood T cells. (Reference: Wan W, Lionakis MS, Liu Q et al (2012) Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice. Cardiovasc Res PMID: 23180724).
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