摘要
背景:肾素-血管紧张素系统和它的主要产物血管紧张素II因为高血压治疗变成了药学产业研究的焦点。肾素-血管紧张素系统的上调与心脏病和其后续的器官损伤相关。经典的抑制肾素-血管紧张素系统的方法主要是基于阻止血管紧张素II受体和抑制血管紧张素酶建立的。循环和组织内肾素-血管紧张素系统的概念为药物靶点开启了新的挑战。尽管付出了巨大的努力,在一些情况下肾素-血管紧张素系统的控制仍然受不理想的副作用和治疗抵抗的限制。 目的:为了提高经典肾素-血管紧张素系统抑制剂的效率,必须阐明由其内部的反馈电路发出的特定并发症。除此之外,用于鉴定血管紧张素II的生物合成途径和对血管紧张素1-7/MAS通路具有相反作用的新肽酶正在做临床应用的测试。这篇综述的目的在于引起基于RNA干扰的控制肾素-血管紧张素系统的新工具的注意。RNAi是抑制mRNA翻译的一种小的非编码核酸。这种方法的有用性已经在肿瘤治疗得到了证实并且也在心血管治疗的领域中取得了进展。 结论:我们认为在不就的将来,除了传统的药理学工具,RNAi也将会用于控制肾素-血管紧张素系统和血管紧张素II的产生。RNAi也将在传统化学药物不容易控制的组织肾素-血管紧张素系统中发挥重要作用。
关键词: 小分子干涉RNA
Current Medicinal Chemistry
Title:Angiotensin II in the Human Physiology: Novel Ways for Synthetic Compounds Utilization
Volume: 23 Issue: 42
Author(s): Iveta Herichová
Affiliation:
关键词: 小分子干涉RNA
摘要: Background: Renin-angiotensin system (RAS) and its main product Angiotensin II (AngII) are in the focus of the pharmacological industry mainly because of hypertension treatment. Up-regulated RAS is generally associated with cardiovascular diseases and consequent organs injuries. The classic inhibition of RAS is based on the blocking of the type 1 AngII receptors and inhibition of ACE. The concept of the circulating and tissue RAS opens new challenges for the drug targeting. In spite of a big effort invested, in some cases a traditional RAS manipulation is struggling with unwanted side effects and/or resistance to treatment.
Objective: To improve the efficiency of the classic RAS inhibitors specific complications issuing from feed-back circuits inside the RAS have to be elucidated. Moreover, new peptidases identified in the AngII biosynthesis and Angiotensin 1-7/MAS pathways with opposing effects to AngII are tested for the clinical use. The aim of this review is also to bring attention to new tools in RAS manipulation based on the RNA interference (RNAi). RNAi employs small non-coding nucleic acids that interfere with the mRNA translation. The usefulness of this approach has been demonstrated in the treatment of oncological diseases and progress was also made in the field of the cardiovascular medicine.
Conclusion: We suppose that in the near future, in addition to traditional pharmacological tools, RNAi will contribute to the control of RAS and AngII production. RNAi may also be of importance in the manipulation of tissue RAS that is not easily accessible by the traditional chemical substances.
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Cite this article as:
Iveta Herichová , Angiotensin II in the Human Physiology: Novel Ways for Synthetic Compounds Utilization, Current Medicinal Chemistry 2016; 23 (42) . https://dx.doi.org/10.2174/0929867323666161014144552
DOI https://dx.doi.org/10.2174/0929867323666161014144552 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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