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中性肽链内切酶:动脉高血压的一个潜在治疗靶点?

Neprilysin: A Potential Therapeutic Target of Arterial Hypertension?

作者信息

Salazar Juan, Rojas-Quintero Joselyn, Cano Clímaco, Pérez José L, Ramírez Paola, Carrasquero Rubén, Torres Wheeler, Espinoza Cristobal, Chacín-González Maricarmen, Bermúdez Valmore

机构信息

Endocrine and Metabolic Disease Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela.

Pulmonary and Critical Care Medicine Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.

出版信息

Curr Cardiol Rev. 2020;16(1):25-35. doi: 10.2174/1573403X15666190625160352.

Abstract

Arterial hypertension is the most prevalent chronic disease in the adult population of developed countries and it constitutes a significant risk factor in the development of cardiovascular disease, contributing to the emergence of many comorbidities, among which heart failure excels, a clinical syndrome that nowadays represents a major health problem with uncountable hospitalizations and the indolent course of which progressively worsens until quality of life decreases and lastly death occurs prematurely. In the light of this growing menace, each day more efforts are invested in the field of cardiovascular pharmacology, searching for new therapeutic options that allow us to modulate the physiological systems that appear among these pathologies. Therefore, in the later years, the study of natriuretic peptides has become so relevant, which mediate beneficial effects at the cardiovascular level such as diuresis, natriuresis, and decreasing cardiac remodeling; their metabolism is mediated by neprilysin, a metalloproteinase, widely expressed in the human and capable of catalyzing many substrates. The modulation of these functions has been studied by decades, giving room to Sacubitril, the first neprilysin inhibitor, which in conjunction with an angiotensin receptor blocker has provided a high efficacy and tolerability among patients with heart failure, for whom it has already been approved and recommended. Nonetheless, in the matter of arterial hypertension, significant findings have arisen that demonstrate the potential role that it will play among the pharmacological alternatives in the upcoming years.

摘要

动脉高血压是发达国家成年人群中最普遍的慢性病,它是心血管疾病发展的一个重要危险因素,会引发许多合并症,其中心力衰竭最为突出,这是一种临床综合征,如今已成为一个重大的健康问题,导致无数次住院治疗,其病程缓慢进展,直至生活质量下降,最终过早死亡。鉴于这种日益严重的威胁,心血管药理学领域投入了越来越多的努力,寻找新的治疗方案,以便我们能够调节这些病理过程中出现的生理系统。因此,近年来,利钠肽的研究变得非常重要,它们在心血管水平上介导诸如利尿、利钠和减少心脏重塑等有益作用;它们的代谢由中性肽链内切酶介导,这是一种金属蛋白酶,在人体内广泛表达,能够催化多种底物。对这些功能的调节已经研究了数十年,催生出了首个中性肽链内切酶抑制剂沙库巴曲,它与血管紧张素受体阻滞剂联合使用,在心力衰竭患者中显示出了高疗效和耐受性,已被批准并推荐用于此类患者。尽管如此,在动脉高血压方面,已经出现了一些重要发现,证明了它在未来几年药理学替代方案中将发挥的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6708/7062041/6ccca4fc85eb/CCR-16-25_F1.jpg

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