血管生成
血管生成素
信号转导
受体酪氨酸激酶
生物
炎症
癌症
癌症研究
安格普特4
医学
内分泌学
内科学
生物信息学
血管内皮生长因子
免疫学
细胞生物学
基因
生物化学
血管内皮生长因子受体
作者
Giuseppina Nicolini,Francesca Forini,Claudia Kusmic,Giorgio Iervasi,Silvana Balzan
出处
期刊:Life Sciences
[Elsevier]
日期:2019-12-01
卷期号:239: 117080-117080
被引量:27
标识
DOI:10.1016/j.lfs.2019.117080
摘要
The angiopoietin signal transduction system is a complex of vascular-specific kinase pathways that plays a crucial role in angiogenesis and maintenance of vascular homeostasis. Angiopoietin1 (Ang1) and 2 (Ang2), the ligand proteins of the pathway, belong to a family of glycoproteins that signal primarily through the transmembrane Tyrosine-kinase-2 receptor. Despite a considerable sequence homology, Ang1 and Ang2 manifest antagonistic effects in pathophysiological conditions. While Ang1 promotes the activation of survival pathways and the stabilization of the normal mature vessels, Ang2 can either favor vessel destabilization and leakage or promote abnormal EC proliferation in a context-dependent manner. Altered Ang1/Ang2 balance has been reported in various pathological conditions in association with inflammation and deregulated angiogenesis. In particular, increased Ang2 levels have been documented in human cancer and cardiovascular disease (CVD), including ischemic myocardial injury, heart failure and other cardiovascular complications secondary to diabetes, chronic renal damage and hypertension. Despite the obvious phenotypic differences, CVD and cancer share some common Ang2-dependent etiopathological mechanisms such as inflammation, epithelial (or endothelial) to mesenchymal transition, and adverse vascular network remodeling. Interestingly, both cancer and CVD are negatively affected by thyroid hormone dyshomeostasis. This review provides an overview of the complex Ang2-dependent signaling involved in CVD and cancer, as well as a survey of the related clinical literature. Moreover, on the basis of recent molecular acquisitions in an experimental model of post ischemic cardiac disease, the putative novel role of the thyroid hormone in the regulation of Ang1/Ang2 balance is also briefly discussed.
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