Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target.
Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target.
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DOI：
10.4172/2329-6607.1000204
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Tian, J
中科院分区：
文献类型：
--
作者：
Fan, X;Xie, J;Tian, J
心脏纤维化是心脏疾病常见的病理过程，可导致心力衰竭。即使在那些没有心脏症状的人中，它也可以导致猝死。组织纤维化可分为两类：替代性纤维化(又称修复性纤维化)和反应性纤维化。在替代性纤维化中，炎症细胞的浸润和细胞外基质(ECM)蛋白的积聚是急性心脏损伤和心肌细胞坏死后形成瘢痕样纤维组织的最初步骤。反应性纤维化可在荷尔蒙变化和压力或容量超负荷的情况下形成。在动物身上的实验研究已经确定了促进纤维化形成的重要途径，如肾素-血管紧张素-醛固酮系统(RAAS)和内皮素途径。尽管使用RAAS抑制剂作为减少心脏纤维化和改善心脏功能的治疗方法的临床试验一直很有希望，但心力衰竭仍然是美国的主要死亡原因。在过去的几十年里，人们在寻找新的靶点和开发治疗心脏纤维化和心力衰竭的新方法方面做出了密集的努力。Na/K-ATPase是一种典型的离子转运体，也被证明具有信号转导的作用，而且Na/K-ATPase信号的长时间激活也被发现促进了心肌纤维化的形成。阻断Na/K-ATPase信号通路激活的新工具已经被开发出来，并显示出在减少心脏纤维化方面的前景。本文将讨论新的分子靶点的最新进展，重点是Na/K-ATPase信号复合体作为治疗心肌纤维化的靶点。
Cardiac fibrosis is a common pathological process in cardiac disease and may lead to heart failure. It can also cause sudden death even in those without cardiac symptoms. Tissue fibrosis can be categorized into two categories: replacement fibrosis (also called reparative fibrosis) and reactive fibrosis. In replacement fibrosis, infiltration of inflammatory cells and accumulation of Extracellular Matrix (ECM) proteins are the initial steps in forming scarlike fibrotic tissue after acute cardiac injury and cardiac cell necrosis. Reactive fibrosis can be formed in response to hormonal change and pressure or volume overload. Experimental studies in animals have identified important pathways such as the Renin-Angiotensin-Aldosterone System (RAAS) and the endothelin pathway that contribute to fibrosis formation. Despite the fact that clinical trials using RAAS inhibitors as therapies for reducing cardiac fibrosis and improving cardiac function have been promising, heart failure is still the leading cause of deaths in the United States. Intensive efforts have been made to find novel targets and to develop new treatments for cardiac fibrosis and heart failure in the past few decades. The Na/K-ATPase, a canonical ion transporter, has been shown to also function as a signal transducer and prolonged activation of Na/K-ATPase signaling has been found to promote the formation of cardiac fibrosis. Novel tools that block the activation of Na/K-ATPase signaling have been developed and have shown promise in reducing cardiac fibrosis. This review will discuss the recent development of novel molecular targets, focusing on the Na/K-ATPase signaling complex as a therapeutic target in treatment of cardiac fibrosis.