From the Centro Cardiologico Monzino, IRCCS, Milano, Italy.
Arterioscler Thromb Vasc Biol. 2019 Jul;39(7):1330-1342. doi: 10.1161/ATVBAHA.119.312612. Epub 2019 May 16.
Clinical and preclinical studies over the past 3 decades have uncovered a multitude of signaling pathways involved in the initiation and progression of atherosclerosis. From these studies, signaling by proteins of the Wnt family has recently emerged as an important player in the development of atherosclerosis. Wnt signaling is characterized by a large number of ligands, receptors, and coreceptors and can be regulated at many different levels. Among Wnt modulators, the evolutionary conserved Dkk (Dickkopf) proteins, and especially Dkk-1, the founding member of the family, are the best characterized. The role of Dkks in the pathophysiology of the arterial wall is only partially understood, but their involvement in atherosclerosis is becoming increasingly evident. This review introduces recent key findings on Dkk proteins and their functions in atherosclerosis and discusses the potential importance of modulating Dkk signaling as part of a novel, improved strategy for preventing and treating atherosclerosis-related diseases. Visual Overview- An online visual overview is available for this article.
在过去的 30 年中,临床和临床前研究揭示了许多参与动脉粥样硬化发生和发展的信号通路。最近,从这些研究中发现,Wnt 家族的蛋白质信号在动脉粥样硬化的发展中是一个重要的参与者。Wnt 信号转导的特点是有大量的配体、受体和辅助受体,并且可以在许多不同的水平上进行调节。在 Wnt 调节剂中,进化保守的 Dkk(Dickkopf)蛋白,尤其是家族的创始成员 Dkk-1,是研究最充分的。Dkks 在动脉壁病理生理学中的作用仅部分被理解,但它们在动脉粥样硬化中的作用越来越明显。这篇综述介绍了 Dkk 蛋白的最新关键发现及其在动脉粥样硬化中的功能,并讨论了调节 Dkk 信号作为预防和治疗与动脉粥样硬化相关疾病的新的、改进的策略的一部分的潜在重要性。