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动脉粥样硬化中的关键趋化因子途径及其治疗潜力。

Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential.

作者信息

Márquez Andrea Bonnin, van der Vorst Emiel P C, Maas Sanne L

机构信息

Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.

Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany.

出版信息

J Clin Med. 2021 Aug 26;10(17):3825. doi: 10.3390/jcm10173825.

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.

摘要

由于心血管疾病(CVDs)仍是全球主要死因,因此改进预防或治疗心血管疾病疗法的探索仍在继续。在此,心血管疾病的主要病因——动脉粥样硬化及其预防成为核心议题。长期以来,趋化因子及其受体在动脉粥样硬化的病理生理发展过程中发挥着重要作用。它们的作用贯穿动脉粥样硬化病变从起始到进展,甚至潜在消退的全过程。因此,这些动脉粥样硬化中的重要调节因子显然是治疗策略开发的靶点。大量临床前研究通过包括竞争性配体和微小RNA在内的各种方法评估了靶向趋化因子信号传导的各种可能性,这些方法在改善动脉粥样硬化方面已显示出有前景的结果。该领域的进展还包括使用靶向特定趋化因子受体的示踪剂进行详细成像。最后,临床试验揭示了各种疗法的潜力,但在开始临床应用之前仍需进一步研究。尽管仍有许多有待了解和研究的内容,但很明显趋化因子及其受体是有吸引力但极其复杂的治疗靶点。因此,本综述将概述各种趋化因子及其受体与动脉粥样硬化之间的联系。还将探讨包括应对这种复杂相互作用的小鼠模型和临床试验在内的不同进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0231/8432216/2d9ccb85089e/jcm-10-03825-g001.jpg

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