Enevoldsen Frederik C, Sahana Jayashree, Wehland Markus, Grimm Daniela, Infanger Manfred, Krüger Marcus
Department of Biomedicine, Aarhus University, Høegh-Guldbergsgade 10, 8000 Aarhus C, Denmark.
Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
J Clin Med. 2020 Mar 18;9(3):824. doi: 10.3390/jcm9030824.
The endothelin axis, recognized for its vasoconstrictive action, plays a central role in the pathology of pulmonary arterial hypertension (PAH). Treatment with approved endothelin receptor antagonists (ERAs), such as bosentan, ambrisentan, or macitentan, slow down PAH progression and relieves symptoms. Several findings have indicated that endothelin is further involved in the pathogenesis of certain other diseases, making ERAs potentially beneficial in the treatment of various conditions. In addition to PAH, this review summarizes the use and perspectives of ERAs in cancer, renal disease, fibrotic disorders, systemic scleroderma, vasospasm, and pain management. Bosentan has proven to be effective in systemic sclerosis PAH and in decreasing the development of vasospasm-related digital ulcers. The selective ERA clazosentan has been shown to be effective in preventing cerebral vasospasm and delaying ischemic neurological deficits and new infarcts. Furthermore, in the SONAR (Study Of Diabetic Nephropathy With Atrasentan) trial, the selective ERA atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease. These data suggest atrasentan as a new therapy in the treatment of diabetic nephropathy and possibly other renal diseases. Preclinical studies regarding heart failure, cancer, and fibrotic diseases have demonstrated promising effects, but clinical trials have not yet produced measurable results. Nevertheless, the potential benefits of ERAs may not be fully realized.
内皮素轴因其血管收缩作用而被人们所熟知，在肺动脉高压（PAH）的病理过程中起着核心作用。使用已获批的内皮素受体拮抗剂（ERA）进行治疗，如波生坦、安立生坦或马昔腾坦，可减缓PAH的进展并缓解症状。多项研究结果表明，内皮素还参与了某些其他疾病的发病机制，这使得ERA在治疗多种病症方面可能具有益处。除PAH外，本综述总结了ERA在癌症、肾脏疾病、纤维化疾病、系统性硬化症、血管痉挛和疼痛管理中的应用及前景。波生坦已被证明对系统性硬化症相关PAH有效，并可减少与血管痉挛相关的指端溃疡的发生。选择性ERA克拉生坦已被证明在预防脑血管痉挛、延缓缺血性神经功能缺损和新梗死方面有效。此外，在SONAR（阿曲生坦治疗糖尿病肾病研究）试验中，选择性ERA阿曲生坦降低了糖尿病和慢性肾脏病患者发生肾脏事件的风险。这些数据表明阿曲生坦可作为治疗糖尿病肾病及可能的其他肾脏疾病的一种新疗法。关于心力衰竭、癌症和纤维化疾病的临床前研究已显示出有前景的效果，但临床试验尚未产生可衡量的结果。然而，ERA的潜在益处可能尚未完全实现。
