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.

中文翻译：

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心脏和血管疾病中的WNT信号传导

WNT信号传导是由多个信号传导分子介导的信号传导途径的详尽而复杂的集合。WNT信号对于包括细胞增殖，分化和组织模式在内的发育过程至关重要。健康成年人的心血管系统中几乎没有WNT信号传导活性，但是在心脏和血管的许多病理中都观察到了该途径的重新激活。这些病理学的高度流行及其对人类疾病负担的重大贡献，引起了人们对WNT信号作为治疗干预潜在靶点的兴趣。在这篇综述中，我们将首先关注该途径的组成及其调控以及不同的信号传导途径。随后，研究了WNT信号在心血管发育中的作用，其次是对其参与血管和心脏疾病的详细讨论。在强调了WNT之间的串扰之后，将生长因子转化为β和血管紧张素II信号传导，以及WNT信号传导在干细胞调节中的新兴作用，我们提供了以不同水平靶向该途径的药物的概述。从合并的研究中，我们得出结论，尽管有时会有相互矛盾的实验数据，但总的情况是，过度刺激WNT信号传导会对心血管病理产生不利影响。迅速增加的不同WNT信号水平干扰药物的收集将允许评估相关心血管疾病动物模型以及最终在不久的患者中对该途径的治疗性干预，从而将许多临床前研究的结果转化为临床研究相关上下文。