van der Vorst Emiel P C, Döring Yvonne, Weber Christian
Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstr 9, 80336, Munich, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
J Mol Med (Berl). 2015 Sep;93(9):963-71. doi: 10.1007/s00109-015-1317-8. Epub 2015 Jul 15.
Atherosclerosis, a chronic inflammatory disease of the medium- and large-sized arteries, is the main underlying cause of cardiovascular diseases (CVDs) most often leading to a myocardial infarction or stroke. However, atherosclerosis can also develop without this clinical manifestation. The pathophysiology of atherosclerosis is very complex and consists of many cells and molecules interacting with each other. Over the last years, chemokines (small 8-12 kDa cytokines with chemotactic properties) have been identified as key players in atherogenesis. However, this remains a very active and dynamic field of research. Here, we will give an overview of the current knowledge about the involvement of chemokines in all phases of atherosclerotic lesion development. Furthermore, we will focus on two chemokines that recently have been associated with atherogenesis, CXCL12, and macrophage migration inhibitory factor (MIF). Both chemokines play a crucial role in leukocyte recruitment and arrest, a critical step in atherosclerosis development. MIF has shown to be a more pro-inflammatory and thus pro-atherogenic chemokine, instead CXCL12 seems to have a more protective function. However, results about this protective role are still quite debatable. Future research will further elucidate the precise role of these chemokines in atherosclerosis and determine the potential of chemokine-based therapies.
动脉粥样硬化是一种发生于中、大动脉的慢性炎症性疾病,是心血管疾病(CVD)的主要潜在病因,常导致心肌梗死或中风。然而,动脉粥样硬化也可能在没有这种临床表现的情况下发生。动脉粥样硬化的病理生理学非常复杂,由许多相互作用的细胞和分子组成。在过去几年中,趋化因子(具有趋化特性的8 - 12 kDa小分子细胞因子)已被确定为动脉粥样硬化发生过程中的关键因素。然而,这仍然是一个非常活跃和动态的研究领域。在这里,我们将概述目前关于趋化因子在动脉粥样硬化病变发展各阶段所起作用的知识。此外,我们将重点关注最近与动脉粥样硬化发生相关的两种趋化因子,即CXCL12和巨噬细胞移动抑制因子(MIF)。这两种趋化因子在白细胞募集和滞留中起关键作用,而白细胞募集和滞留是动脉粥样硬化发展中的关键步骤。MIF已被证明是一种更具促炎作用从而促动脉粥样硬化的趋化因子,而CXCL12似乎具有更具保护作用。然而,关于这种保护作用的结果仍存在很大争议。未来的研究将进一步阐明这些趋化因子在动脉粥样硬化中的精确作用,并确定基于趋化因子的治疗潜力。