Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential

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.

Circ-MBOAT2 Regulates Angiogenesis via the miR-495/NOTCH1 Axis and Associates with Myocardial Perfusion in Patients with Coronary Chronic Total Occlusion

“…Chemokines pathways have long been known to play an important role in the pathophysiological development of cardiovascular diseases [10]. As a sub-type of cardiovascular disease, CTO has received a lot of attention from scientific researchers.…”

A Common Variant at the 3'untranslated Region of the CCL7 Gene (rs17735770) Is Associated With Decreased Susceptibility to Coronary Heart Disease

“…Our findings invite to revisit the experimentation on therapeutic approaches based on CCR2 antagonists for the prevention of cardiovascular disease. Because their influence in inflammation and monocyte biology, chemokines and their receptors have been the subject of pharmaceutical targeting for atherosclerosis and related conditions in recent years ( 62 ). In murine preclinical models of atherosclerosis, both directed antagonism to either CCR2 or a subset of chemokine receptors, including CCR2, result in a reduction in plaque formation ( 63 , 64 ).…”

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients—A Review: Part I—Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients

“…Plaque rupture and thrombotic occlusion are typical in coronary arteries; however, they are less commonly seen in internal carotid artery stenosis (ICAS) and account for only 10–20% of ischemic strokes [ 44 , 45 ]. In the case of ICAS, a more common etiology of stroke is the embolization of cerebral arteries with detached fragments of atherosclerotic plaque (seen in approximately 70–80% of strokes associated with ICAS) [ 46 ]. Risk factors for cerebral ischemia associated with atherosclerotic plaque include inflammation within the plaque (e.g., MMP-9 concentration predicts the occurrence of cerebral ischemia), large plaque surface area (over 40 mm 2 ), ulceration of its surface, a high lipid-necrotic load, and the presence of plaque vascularization (angiogenesis) [ 46 , 47 ].…”