Angiotensin II and Vascular Injury
Angiotensin II and Vascular Injury
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DOI：
10.1007/s11906-014-0431-2
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发表时间：
2014-06-01
影响因子：
5.6
通讯作者：
Touyz, Rhian M.
中科院分区：
文献类型：
--
作者：
Montezano, Augusto C.;Aurelie Nguyen Dinh Cat;Touyz, Rhian M.
血管损伤在心血管疾病中起着重要作用，其特征在于内皮功能障碍、结构重塑、炎症和纤维化。导致这一现象的细胞过程包括血管平滑肌细胞（VSMC）生长/凋亡的改变、纤维化、收缩力增加和血管钙化。与这些事件相关的是VSMC分化和从收缩型表型到增殖/分泌型表型的表型转换。与巨噬细胞浸润和氧化还原敏感性促炎基因表达增加相关的炎症也有助于血管重塑。血管紧张素II是参与血管损伤的众多因素之一。血管紧张素II，以前被认为是肾素-血管紧张素系统（RAS）的唯一生物活性下游肽，被转化为更小的肽，[血管紧张素III，血管紧张素IV，血管紧张素-（1-7）]，其是功能性的，并且调节血管张力和结构。Ang II的作用是通过与AT（1）R和AT（2）R结合后激活的信号通路介导的。AT（1）R激活通过PLC-IP 3-DAG、MAP激酶、酪氨酸激酶、酪氨酸磷酸酶和RhoA/Rho激酶诱导效应。血管紧张素II通过激活血管NAD（P）H氧化酶（Nox）刺激活性氧（ROS）的产生而发挥其多种病理生理作用。ROS反过来影响氧化还原敏感的信号分子。在这里，我们讨论了血管紧张素II在血管损伤中的作用，侧重于分子机制和细胞过程。血管重塑，炎症，钙化和动脉粥样硬化的影响突出。
Vascular injury, characterized by endothelial dysfunction, structural remodelling, inflammation and fibrosis, plays an important role in cardiovascular diseases. Cellular processes underlying this include altered vascular smooth muscle cell (VSMC) growth/apoptosis, fibrosis, increased contractility and vascular calcification. Associated with these events is VSMC differentiation and phenotypic switching from a contractile to a proliferative/secretory phenotype. Inflammation, associated with macrophage infiltration and increased expression of redox-sensitive pro-inflammatory genes, also contributes to vascular remodelling. Among the many factors involved in vascular injury is Ang II. Ang II, previously thought to be the sole biologically active downstream peptide of the renin-angiotensin system (RAS), is converted to smaller peptides, [Ang III, Ang IV, Ang-(1-7)], that are functional and that modulate vascular tone and structure. The actions of Ang II are mediated via signalling pathways activated upon binding to AT(1)R and AT(2)R. AT(1)R activation induces effects through PLC-IP3-DAG, MAP kinases, tyrosine kinases, tyrosine phosphatases and RhoA/Rho kinase. Ang II elicits many of its (patho)physiological actions by stimulating reactive oxygen species (ROS) generation through activation of vascular NAD(P)H oxidase (Nox). ROS in turn influence redox-sensitive signalling molecules. Here we discuss the role of Ang II in vascular injury, focusing on molecular mechanisms and cellular processes. Implications in vascular remodelling, inflammation, calcification and atherosclerosis are highlighted.