Atherosclerosis: current pathogenesis and therapeutic options

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Abstract

Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their receptors. New pro- and anti-inflammatory pathways linking lipid and inflammation biology have been discovered, and genetic profiling studies have unveiled variations involved in human CAD. The growing understanding of the inflammatory processes and mediators has uncovered an intriguing diversity of targetable mechanisms that can be exploited to complement lipid-lowering therapies. Here we aim to systematically survey recently identified molecular mechanisms, translational developments and clinical strategies for targeting lipid-related inflammation in atherosclerosis and CAD.

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Figure 1: Role of chemokines and their receptors in atherogenesis.
Figure 2: Neutrophils as crucial players in atherogenesis.
Figure 3: DCs at the crossroads of adaptive immunity.
Figure 4: Lipid mediators affect inflammation and atherogenesis through diverse signaling pathways.

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Acknowledgements

This work was supported by Deutsche Forschungsgemeinschaft (FOR809), the European Research Council and Fondation Leducq. We sincerely apologize to all scientists whose important contributions to the field could not be cited due to space limitations.

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Correspondence to Christian Weber.

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C.W. is shareholder of Carolus Therapeutics Inc.

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