New perspectives for the treatment of pulmonary hypertension.
New perspectives for the treatment of pulmonary hypertension.
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DOI：
10.1111/j.1476-5381.2010.01164.x
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发表时间：
2011-05
影响因子：
7.3
通讯作者：
Hobbs AJ
中科院分区：
文献类型：
--
作者：
Baliga RS;MacAllister RJ;Hobbs AJ
肺动脉高压（PH）是一种预后不良的衰弱性疾病。尽管在过去15年中引入了前列环素类似物、内皮素受体拮抗剂和磷酸二酯酶5抑制剂，但治疗选择仍然有限；这些干预措施主要针对与病情相关的内皮和血管功能障碍，但只是延迟疾病的进展，而不是提供治愈。为了提高疗效，新兴的方法集中在促增殖表型上，促增殖表型支持肺血管重构，并导致循环受损和右心衰。许多新的靶点已经在PH动物模型中被研究和验证，包括鸟苷酸环化酶、磷酸二酯酶、酪氨酸激酶、Rho激酶、骨形态发生蛋白信号传导、5-羟色胺、过氧化物酶体增殖物激活物受体和离子通道的调节。此外，利用和优化血管扩张剂和抗增殖特性的这些治疗方法的组合将提供进一步的，可能是协同的，提高疗效的希望；针对右心的治疗也可能带来额外的好处。这篇综述强调了当前的治疗选择，有希望的新疗法，并提供了联合治疗疾病的基本原理。这篇文章是呼吸药理学主题的一部分。要查看本期的其他文章，请访问http://dx.doi.org/10.1111/bph.2011.163.issue-1
Pulmonary hypertension (PH) is a debilitating disease with a poor prognosis. Therapeutic options remain limited despite the introduction of prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase 5 inhibitors within the last 15 years; these interventions address predominantly the endothelial and vascular dysfunctionS associated with the condition, but simply delay progression of the disease rather than offer a cure. In an attempt to improve efficacy, emerging approaches have focused on targeting the pro-proliferative phenotype that underpins the pulmonary vascular remodelling in the lung and contributes to the impaired circulation and right heart failure. Many novel targets have been investigated and validated in animal models of PH, including modulation of guanylate cyclases, phosphodiesterases, tyrosine kinases, Rho kinase, bone morphogenetic proteins signalling, 5-HT, peroxisome proliferator activator receptors and ion channels. In addition, there is hope that combinations of such treatments, harnessing and optimizing vasodilator and anti-proliferative properties, will provide a further, possibly synergistic, increase in efficacy; therapies directed at the right heart may also offer an additional benefit. This overview highlights current therapeutic options, promising new therapies, and provides the rationale for a combination approach to treat the disease. This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1
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