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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Therapeutic potential of the epidermal growth factor receptor transactivation in hypertension: a convergent signaling pathway of vascular tone, oxidative stress, and hypertrophic growth downstream of vasoactive G-protein-coupled receptors?
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Therapeutic potential of the epidermal growth factor receptor transactivation in hypertension: a convergent signaling pathway of vascular tone, oxidative stress, and hypertrophic growth downstream of vasoactive G-protein-coupled receptors?

机译:表皮生长因子受体反式激活在高血压中的治疗潜力:血管活性G蛋白偶联受体下游的血管紧张,氧化应激和肥大生长的收敛信号通路?

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摘要

The concurrence of enhanced vascular tone, oxidative stress, and hypertrophic growth is a hallmark of hypertension, the condition characterized by sustained elevated blood pressure. However, it is unclear how and why such apparently distinct processes coincide in hypertension. Elevated levels of certain vasoactive G-protein-coupled receptor agonists (such as catecholamines, endothelin-1, and angiotensin II) can explain, at least in part, the development and progression of many hypertensive disorders. Here, we review findings made by other investigators and ourselves suggesting that enhanced vascular tone, oxidative stress, and hypertrophic growth characteristically induced by these agonists involve the transactivation of growth factor receptors. The first step in this transactivation mechanism is agonist-induced activation of metalloproteinase-dependent shedding of growth factors. Shed growth factors then trigger intracellular signaling cascades necessary for growth, production of reactive oxygen species, and maintenance of vascular tone. If this hypothesis is proven generally correct, then transactivation blockers have general therapeutic potential in hypertension regardless of the causative agonist.
机译:血管紧张性,氧化应激和肥厚性生长增强的并存是高血压的标志,高血压的特征是持续升高的血压。但是,尚不清楚在高血压中这种明显不同的过程如何以及为什么同时发生。某些血管活性G蛋白偶联受体激动剂(例如儿茶酚胺,内皮素-1和血管紧张素II)水平升高,至少可以部分解释许多高血压疾病的发生和发展。在这里,我们回顾了其他研究者和我们自己的发现,这些发现提示这些激动剂特征性地增强了血管张力,氧化应激和肥大性生长,涉及生长因子受体的反式激活。这种反式激活机制的第一步是激动剂诱导的金属蛋白酶依赖性生长因子脱落。然后,脱落的生长因子触发细胞内信号传导级联,这些级联对于生长,活性氧的产生和维持血管张力是必需的。如果这一假设大体上被证明是正确的,那么无论致病性激动剂如何,反式激活阻滞剂在高血压中都有一般的治疗潜力。

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