Regulation of vascular tone by indoleamine 2,3-dioxygenase

吲哚胺 2,3-双加氧酶调节血管张力

• 批准号: nhmrc : 400992
• 负责人: E/Pr Nicholas Hunt
• 金额: $ 30.49万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-vascular-tone-23-dioxygenase/83068
• 关键词: Regulation; vascular; tone; indoleamine; dioxygenase

As part of their normal function, blood vessels dilate and contract, for example in response to the pulsative force with which our heart pumps the blood around the circulation. Blood vessels produce several different chemicals that cause vessel relaxation, and these vary depending on several factors, such as the blood vessel involved, its diameter and precise location within our body. In addition to responding to the pulsative nature of blood flow, blood vessels also respond to many other conditions, including certain diseases, so that it is not surprising that many of the commonly used cardiovascular drugs target to change blood vessel tone, either increasing or decreasing blood pressure, depending on the circumstances involved. The present application is based on the discovery, in the mouse, that during a systemic infection a specific protein is induced in the cells that line blood vessels. This protein degrades a certain amino acid into a novel chemical, called kynurenine. We observed that kynurenine has previously unrecognised vessel-relaxing properties. The present project will investigate the importance of kynurenine formation as a novel pathway in the regulation of vascular tone. Mice, in which the activity of the kynurenine-producing protein will be modulated (both up and down) will be used in conjunction with blood pressure and other relevant measurements. In addition, the role of a unique molecule, called superoxide anion radical, in the production of kynurenine by the protein will also be tested. If our results confirm that the protein and kynurenine are indeed involved in regulating vascular tone, our research could have tremendous impact on many aspects of normal physiology as well as cardiovascular diseases that remain the major single cause of death in Australia.

作为其正常功能的一部分，血管扩张和收缩，例如响应于我们的心脏将血液泵送到循环周围的脉动力。血管产生几种不同的化学物质，导致血管松弛，这些化学物质取决于几个因素，如所涉及的血管，其直径和在我们体内的精确位置。除了对血流的脉动性作出反应外，血管还对许多其他情况作出反应，包括某些疾病，因此许多常用的心血管药物靶向改变血管张力，根据所涉及的情况增加或降低血压，这并不奇怪。本申请基于在小鼠中的发现，即在全身性感染期间，在内衬血管的细胞中诱导特异性蛋白质。这种蛋白质将某种氨基酸降解成一种新的化学物质，称为犬尿氨酸。我们观察到犬尿氨酸具有以前未被认识到的血管舒张特性。本项目将研究犬尿氨酸形成作为血管张力调节的新途径的重要性。其中犬尿氨酸产生蛋白的活性将被调节（上调和下调）的小鼠将与血压和其他相关测量结合使用。此外，还将测试一种称为超氧阴离子自由基的独特分子在蛋白质产生犬尿氨酸中的作用。如果我们的研究结果证实这种蛋白质和犬尿氨酸确实参与调节血管张力，我们的研究可能会对正常生理学的许多方面以及心血管疾病产生巨大影响，这些疾病仍然是澳大利亚主要的单一死亡原因。