A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease.
A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease.
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DOI：
10.3389/fphar.2017.00186
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发表时间：
2017
影响因子：
5.6
通讯作者：
Dart AM
中科院分区：
文献类型：
--
作者：
Fang L;Murphy AJ;Dart AM
心脏纤维化是各种心血管疾病的核心。近年来，对心肌纤维化的机制和治疗靶点的研究取得了很大进展。然而，尽管许多抗纤维化治疗已经在动物模型中进行了研究，似乎很有希望，但将实验结果转化为人类患者的研究结果相当有限。因此，几种在动物模型中显示出减少心脏纤维化的潜在新疗法要么没有在人类身上进行测试，要么在临床试验中被证明是令人失望的。大多数临床研究规模较小，或者没有维持足够长的时间。此外，尽管一些传统疗法，如肾素-血管紧张素-醛固酮系统(RAAS)抑制剂，已被证明可以减少人类的心脏纤维化，但心脏纤维化在心力衰竭患者中仍然存在，即使使用这些传统疗法，这表明需要开发新的和有效的心血管疾病抗纤维化疗法。在这篇综述文章中，我们总结了人类心血管疾病的抗纤维化治疗，讨论了目前使用的治疗方法的局限性，以及导致如此多的抗纤维化药物在临床水平失败的可能原因。然后，我们将探索心血管疾病抗纤维化治疗的未来方向，这将包括显示出希望的新兴抗纤维化药物，如松弛素。需要考虑更好地了解动物模型和人类病理学之间的差异，以及更好地洞察精心设计的关于适当终点和适当剂量的试验，以确定更有效的抗纤维化药物来治疗人类患者的心血管纤维化。
Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials. A majority of clinical studies are of small size or have not been maintained for long enough periods. In addition, although some conventional therapies, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to reduce cardiac fibrosis in humans, cardiac fibrosis persists in patients with heart failure even when treated with these conventional therapies, indicating a need to develop novel and effective anti-fibrotic therapies in cardiovascular disease. In this review article, we summarize anti-fibrotic therapies for cardiovascular disease in humans, discuss the limitations of currently used therapies, along with possible reasons for the failure of so many anti-fibrotic drugs at the clinical level. We will then explore the future directions of anti-fibrotic therapies on cardiovascular disease, and this will include emerging anti-fibrotics that show promise, such as relaxin. A better understanding of the differences between animal models and human pathology, and improved insight into carefully designed trials on appropriate end-points and appropriate dosing need to be considered to identify more effective anti-fibrotics for treating cardiovascular fibrosis in human patients.