Is chymase 1 a therapeutic target in cardiovascular disease?

IF 4.6 2区医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-08-21 DOI:10.1080/14728222.2023.2247561

Carlos M Ferrario, Sarfaraz Ahmad, Robert Speth, Louis J Dell'Italia

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Abstract

Introduction: Non-angiotensin converting enzyme mechanisms of angiotensin II production remain underappreciated in part due to the success of current therapies to ameliorate the impact of primary hypertension and atherosclerotic diseases of the heart and the blood vessels. This review scrutinize the current literature to highlight chymase role as a critical participant in the pathogenesis of cardiovascular disease and heart failure.

Areas covered: We review the contemporaneous understanding of circulating and tissue biotransformation mechanisms of the angiotensins focusing on the role of chymase as an alternate tissue generating pathway for angiotensin II pathological mechanisms of action.

Expert opinion: While robust literature documents the singularity of chymase as an angiotensin II-forming enzyme, particularly when angiotensin converting enzyme is inhibited, this knowledge has not been fully recognized to clinical medicine. This review discusses the limitations of clinical trials' that explored the benefits of chymase inhibition in accounting for the failure to duplicate in humans what has been demonstrated in experimental animals.

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糜蛋白酶1是心血管疾病的治疗靶点吗？

引言：血管紧张素II产生的非血管紧张素转换酶机制仍被低估，部分原因是目前的治疗方法成功地减轻了原发性高血压和心脏血管动脉粥样硬化疾病的影响。这篇综述仔细审查了当前的文献，以强调糜蛋白酶在心血管疾病和心力衰竭发病机制中的重要作用。涵盖的领域：我们回顾了对血管紧张素循环和组织生物转化机制的同期理解，重点是糜蛋白酶作为血管紧张素II病理作用机制的替代组织生成途径的作用。专家意见：虽然大量文献记录了糜蛋白酶作为血管紧张素II形成酶的独特性，特别是当血管紧张素转换酶被抑制时，但这一知识尚未得到临床医学的充分认可。这篇综述讨论了临床试验的局限性，这些试验探索了糜蛋白酶抑制在解释人类未能复制实验动物中证明的结果方面的益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Therapeutic Targets 医学-药学

CiteScore

8.90

自引率

1.70%

发文量

审稿时长

3 months

期刊介绍： The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.