Pharmacology of Pulmonary Arterial Hypertension: An Overview of Current and Emerging Therapies.,ACS Pharmacology & Translational Science

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Pharmacology of Pulmonary Arterial Hypertension: An Overview of Current and Emerging Therapies.
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-07-01 , DOI: 10.1021/acsptsci.0c00048
Monika Spaczyńska ₁ , Susana F Rocha ₁ , Eduardo Oliver _{1,

2}

Affiliation

Pulmonary arterial hypertension is a rare and devastating disease characterized by an abnormal chronic increase in pulmonary arterial pressure above 20 mmHg at rest, with a poor prognosis if not treated. Currently, there is not a single fully effective therapy, even though a dozen of drugs have been developed in the last decades. Pulmonary arterial hypertension is a multifactorial disease, meaning that several molecular mechanisms are implicated in its pathology. The main molecular pathways regulating the pulmonary vasomotor tone—endothelin, nitric oxide, and prostacyclin—are the most biologically and therapeutically explored to date. However, drugs targeting these pathways have already found their limitations. In the last years, translational research and clinical trials have made a strong effort in suggesting and testing novel therapeutic strategies for this disease. These approaches involve targeting the main molecular pathways with novel drugs, drug repurposing for novel targets, and also using combinatorial therapies. In this review, we summarize current strategies and drugs targeting the endothelin, nitric oxide, and prostacyclin pathways, as well as, the emerging new drugs proposed to cope with vascular remodelling, metabolic switch, perivascular inflammation, epigenetic modifications, estrogen deregulation, serotonin, and other neurohumoral mechanisms characteristic of this disease. Nowadays, pulmonary arterial hypertension remains an incurable disease; however, the incoming new knowledge makes us believe that new promising therapies are coming to the clinical arena soon.

中文翻译：

肺动脉高压的药理学：目前和新兴疗法的概述。

肺动脉高压是一种罕见的破坏性疾病，其特征在于，静止时肺动脉压异常慢性升高超过20 mmHg，如果不治疗，其预后不良。尽管在过去的几十年中已经开发了十多种药物，但是目前还没有一种完全有效的疗法。肺动脉高压是一种多因素疾病，这意味着其病理学涉及多种分子机制。迄今为止，调节肺血管舒缩张力的主要分子途径（内皮素，一氧化氮和前列环素）在生物学和治疗上都得到了最深入的探索。但是，靶向这些途径的药物已经发现了其局限性。最近几年转化研究和临床试验在建议和测试这种疾病的新治疗策略方面做出了巨大的努力。这些方法涉及使用新药靶向主要分子途径，重新定位新靶标的药物以及使用组合疗法。在这篇综述中，我们总结了针对内皮素，一氧化氮和前列环素途径的当前策略和药物，以及为应对血管重塑，代谢转换，血管周炎症，表观遗传修饰，雌激素失调，5-羟色胺，以及该疾病的其他神经体液机制。如今，肺动脉高压仍然是无法治愈的疾病。然而，

更新日期：2020-08-14

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