Randell Amy, Daneshtalab Noriko
Health Sciences Center, School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Health Sciences Center, School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
J Am Soc Hypertens. 2017 Jul;11(7):437-448. doi: 10.1016/j.jash.2017.04.010. Epub 2017 May 3.
Elastin microfibril interface-located protein 1 (EMILIN1), a glycoprotein, is associated with elastin in the extracellular matrix (ECM) of arteries, lymph vasculature, and other tissues. EMILIN1 particularly has a niche role in elastin fiber biogenesis (elastogenesis) by aiding with the fusion of elastin fibers, rendering them more ordered. In addition to elastogenesis, EMILIN1 has been shown to have roles in maintenance of vascular cell morphology, smooth muscle cell adhesion to elastic fibers, and transforming growth factor (TGFβ) regulation, by inhibiting TGFβ activation via blocking the proteolytic production of the latency-associated peptide/active TGFβ complex. The increased TGFβ signaling induced during EMILIN1 deficiency alters TGFβ activity, resulting in vascular smooth muscle cell growth and vascular remodeling. The increasing systemic blood pressure associated with TGFβ signaling may be closely linked to the activity of other mediators that affect cardiovascular homeostasis, such as angiotensin II. The increase in prevalence of hypertension and other cardiovascular diseases in other disease states likely involve a complex activation of TGFβ signaling and ECM dysfunction. Thus, the interaction of TGFβ and ECM components appears to be integrative involving both structural alterations to vessels through EMILIN1 and changes in TGFβ signaling processes. This review summarizes the current knowledge on the EMILIN1-TGFβ relationship; the specific roles of EMILIN1 and TGFβ in blood pressure regulation, their synergistic interaction, and in particular the role of TGFβ (in conjunction with ECM proteins) in other disease states altering cardiovascular homeostasis.
弹性微原纤维界面定位蛋白1（EMILIN1）是一种糖蛋白，与动脉、淋巴管系统及其他组织的细胞外基质（ECM）中的弹性蛋白相关。EMILIN1在弹性纤维生物合成（弹性生成）中具有独特作用，它有助于弹性纤维融合，使其更有序。除弹性生成外，EMILIN1还被证明在维持血管细胞形态、平滑肌细胞与弹性纤维的黏附以及转化生长因子（TGFβ）调节中发挥作用，它通过阻断潜伏相关肽/活性TGFβ复合物的蛋白水解产生来抑制TGFβ激活。EMILIN1缺乏时诱导的TGFβ信号增加会改变TGFβ活性，导致血管平滑肌细胞生长和血管重塑。与TGFβ信号相关的系统性血压升高可能与影响心血管稳态的其他介质（如血管紧张素II）的活性密切相关。其他疾病状态下高血压和其他心血管疾病患病率的增加可能涉及TGFβ信号的复杂激活和ECM功能障碍。因此，TGFβ与ECM成分之间的相互作用似乎是综合性的，涉及通过EMILIN1对血管的结构改变以及TGFβ信号传导过程的变化。本综述总结了目前关于EMILIN1 - TGFβ关系的知识；EMILIN1和TGFβ在血压调节中的具体作用、它们的协同相互作用，特别是TGFβ（与ECM蛋白结合）在改变心血管稳态的其他疾病状态中的作用。
