Abstract
The search to improve therapies to prevent or treat cardiovascular diseases (CVDs) rages on, as CVDs remain a leading cause of death worldwide. Here, the main cause of CVDs, atherosclerosis, and its prevention, take center stage. Chemokines and their receptors have long been known to play an important role in the pathophysiological development of atherosclerosis. Their role extends from the initiation to the progression, and even the potential regression of atherosclerotic lesions. These important regulators in atherosclerosis are therefore an obvious target in the development of therapeutic strategies. A plethora of preclinical studies have assessed various possibilities for targeting chemokine signaling via various approaches, including competitive ligands and microRNAs, which have shown promising results in ameliorating atherosclerosis. Developments in the field also include detailed imaging with tracers that target specific chemokine receptors. Lastly, clinical trials revealed the potential of various therapies but still require further investigation before commencing clinical use. Although there is still a lot to be learned and investigated, it is clear that chemokines and their receptors present attractive yet extremely complex therapeutic targets. Therefore, this review will serve to provide a general overview of the connection between various chemokines and their receptors with atherosclerosis. The different developments, including mouse models and clinical trials that tackle this complex interplay will also be explored.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of death worldwide with an estimated 17.8 million annual deaths according to the Global Burden of Disease Study 2017 [1].Atherosclerosis, a pathology in which inflammation is one of the major driving forces of disease progression, has been recognized as the leading cause of CVDs [2–4]
Chemokines and their receptors are considered to play a significant role in the development and progression of atherosclerosis and CVDs, the appropriate clinical treatments have yet to be approved [4]
The general lack of accepted therapies is caused by a variety of reasons, including problems like the intrinsic redundancy of chemokines and their receptors, insufficient knowledge of the mechanistic roles of receptors and chemokines in disease, the potential to block important modulators of protective and necessary immune responses [174], the inadequate selection of dosage and targets, and the circadian-dependent effect of interventions [175]
Summary
Cardiovascular diseases (CVDs) are the leading cause of death worldwide with an estimated 17.8 million annual deaths according to the Global Burden of Disease Study 2017 [1]. The selectivity of inflammatory targets specific to atherosclerosis has more recently been highlighted by the Cardiovascular Inflammation Reduction Trial (CIRT). Methotrexate was successful in reducing CVD risk in patients with rheumatoid or psoriatic arthritis [8–10], which further supports the selectivity of inflammatory targets and emphasizes the importance of selecting the appropriate inflammatory pathways. Besides these cytokines, chemokines and their receptors are potential targets due to their specific roles in atherosclerotic disease progression [4,11–13]. In this review we present a brief overview of atherosclerosis and chemokines, highlighting the main chemokines involved in the pathogenesis, and discuss ongoing developments to translate these targets into therapeutic strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
