WNT Signaling in Cardiac and Vascular Disease.
WNT Signaling in Cardiac and Vascular Disease.
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DOI：
10.1124/pr.117.013896
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发表时间：
2018-01
影响因子：
21.1
通讯作者：
Blankesteijn WM
中科院分区：
文献类型：
--
作者：
Foulquier S;Daskalopoulos EP;Lluri G;Hermans KCM;Deb A;Blankesteijn WM
WNT信号是由多种信号分子介导的信号转导途径的复杂集合。WNT信号对发育过程至关重要，包括细胞增殖、分化和组织模式。在健康成人的心血管系统中，WNT信号活动很少，但在许多心脏和血管病变中观察到该途径的重新激活。这些病理的高患病率及其对人类疾病负担的重大贡献提高了人们对WNT信号作为治疗干预潜在靶点的兴趣。在本文中，我们首先将重点介绍该通路的组成及其调控以及不同的信号通路。随后，讨论了WNT信号在心血管发育中的作用，随后详细讨论了其在血管和心脏疾病中的作用。在强调了WNT、转化生长因子-β和血管紧张素II信号之间的相互作用，以及WNT信号在干细胞调控中的新作用之后，我们概述了不同水平上靶向该通路的药物。从综合研究中，我们得出结论，尽管有时实验数据相互矛盾，但总体情况正在出现，过度刺激WNT信号会对心血管病理产生不利影响。干扰不同水平WNT信号的药物收集量的迅速增加，将允许在心血管疾病的相关动物模型中评估该途径的治疗干预措施，并最终在不久的将来在患者中进行评估，将许多临床前研究的结果转化为临床相关背景。
WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signaling molecules. WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterning. Little WNT signaling activity is present in the cardiovascular system of healthy adults, but reactivation of the pathway is observed in many pathologies of heart and blood vessels. The high prevalence of these pathologies and their significant contribution to human disease burden has raised interest in WNT signaling as a potential target for therapeutic intervention. In this review, we first will focus on the constituents of the pathway and their regulation and the different signaling routes. Subsequently, the role of WNT signaling in cardiovascular development is addressed, followed by a detailed discussion of its involvement in vascular and cardiac disease. After highlighting the crosstalk between WNT, transforming growth factor-β and angiotensin II signaling, and the emerging role of WNT signaling in the regulation of stem cells, we provide an overview of drugs targeting the pathway at different levels. From the combined studies we conclude that, despite the sometimes conflicting experimental data, a general picture is emerging that excessive stimulation of WNT signaling adversely affects cardiovascular pathology. The rapidly increasing collection of drugs interfering at different levels of WNT signaling will allow the evaluation of therapeutic interventions in the pathway in relevant animal models of cardiovascular diseases and eventually in patients in the near future, translating the outcomes of the many preclinical studies into a clinically relevant context.
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