摘要
钠氢离子交换器和水通道蛋白在病理生理情况下,都是关键的细胞体积和细胞内离子的调节者。特别是亚型1通过直接影响水和离子交换穿过质膜、钠氢离子交换器和水通道蛋白,并对几种类型的刺激反应的应答如高渗应激,可以同时影响血管张力和细胞骨架。钠氢离子交换器1与水通道蛋白1主要在心血管系统中的表达。他们在升高的细胞外液渗透压的过度激活,对微血管和大血管内皮细胞均有害,如糖尿病高血糖的发生。虽然钠氢离子通道泵-1和水通道蛋白1调节细胞内体积和离子,它们也是影响高渗性相关基因的激活和参与葡萄糖毒性及血管损伤细胞的功能。由于对钠氢离子交换器和水通道蛋白参与微血管和大血管疾病,包括高血压和动脉粥样硬化斑块不稳定,研究的重点是开发这些转运蛋白抑制剂。为开发可以治疗糖尿病动脉粥样硬化的新药物,我们回顾现有的水通道蛋白的生物方面和调控机制,包括其潜在目标的研究。
关键词: 水通道蛋白,动脉粥样硬化,糖尿病,高渗应激,钠氢离子交换器。
图形摘要
Current Drug Targets
Title:Aquaporin-1 and Sodium-Hydrogen Exchangers as Pharmacological Targets in Diabetic Atherosclerosis
Volume: 16 Issue: 4
Author(s): Rosalinda Madonna and Raffaele De Caterina
Affiliation:
关键词: 水通道蛋白,动脉粥样硬化,糖尿病,高渗应激,钠氢离子交换器。
摘要: Sodium-hydrogen exchangers (NHEs) and aquaporins (AQPs) are key regulators of cell volume and intracellular ions both in physiological and pathological conditions. By directly affecting water and ion exchanges across the plasma membrane, NHEs and AQPs, particularly isoforms 1, can also influence vascular tone and the cytoskeleton, respectively, in response to several types of stimuli, such as hypertonic stress. NHE-1 and AQP1 are mainly expressed in tissues of the cardiovascular system. Their excessive activation in response to elevated extracellular osmolarity, as occurring in diabetic hyperglycemia, can be deleterious both for micro- and macrovascular endothelial cells. Although NHE-1 and AQP1 regulate the intracellular volume and ions, they also influence the activation of hypertonicity-responsive genes and cell functions involved in glucotoxicity and vascular injury. Because of the involvement of NHEs and AQPs in micro- and macrovascular disease, including arterial hypertension and atherosclerotic plaque destabilization, research has focused on developing inhibitors of these transporters. We here review current knowledge of NHEs and AQPs investigating biological aspects and mechanisms of their regulation, including their potential as target for developing new drugs that could target diabetic atherosclerosis.
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Cite this article as:
Rosalinda Madonna and Raffaele De Caterina , Aquaporin-1 and Sodium-Hydrogen Exchangers as Pharmacological Targets in Diabetic Atherosclerosis, Current Drug Targets 2015; 16 (4) . https://dx.doi.org/10.2174/1389450116666141219115720
DOI https://dx.doi.org/10.2174/1389450116666141219115720 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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