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首页> 外文期刊>American Journal of Physiology >Minoxidil improves vascular compliance, restores cerebral blood flow, and alters extracellular matrix gene expression in a model of chronic vascular stiffness
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Minoxidil improves vascular compliance, restores cerebral blood flow, and alters extracellular matrix gene expression in a model of chronic vascular stiffness

机译：米诺伊尔改善血管顺应性，恢复脑血流量，并在慢性血管刚度模型中改变细胞外基质基因表达

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Increased vascular stiffness correlates with a higher risk of cardiovascular complications in aging adults. Elastin (ELN) insufficiency, as observed in patients with Williams-Beuren syndrome or with familial supravalvular aortic stenosis, also increases vascular stiffness and leads to arterial narrowing. We used Eln+/? mice to test the hypothesis that pathologically increased vascular stiffness with concomitant arterial narrowing leads to decreased blood flow to end organs such as the brain. We also hypothesized that drugs that remodel arteries and increase lumen diameter would improve flow. To test these hypotheses, we compared carotid blood flow using ultrasound and cerebral blood flow using MRI-based arterial spin labeling in wild-type (WT) and Eln+/? mice. We then studied how minoxidil, an ATP-sensitive K+ channel opener and vasodilator, affects vessel mechanics, blood flow, and gene expression. Both carotid and cerebral blood flows were lower in Eln+/? mice than in WT mice. Treatment of Eln+/? mice with minoxidil lowered blood pressure and reduced functional arterial stiffness to WT levels. Minoxidil also improved arterial diameter and restored carotid and cerebral blood flows in Eln+/? mice. The beneficial effects persisted for weeks after drug removal. RNA-Seq analysis revealed differential expression of 127 extracellular matrix-related genes among the treatment groups. These results indicate that ELN insufficiency impairs end-organ perfusion, which may contribute to the increased cardiovascular risk. Minoxidil, despite lowering blood pressure, improves end-organ perfusion. Changes in matrix gene expression and persistence of treatment effects after drug withdrawal suggest arterial remodeling. Such remodeling may benefit patients with genetic or age-dependent ELN insufficiency.NEW & NOTEWORTHY Our work with a model of chronic vascular stiffness, the elastin (Eln)+/? mouse, shows reduced brain perfusion as measured by carotid ultrasound and MRI arterial spin labeling. Vessel caliber, functional stiffness, and blood flow improved with minoxidil. The ATP-sensitive K+ channel opener increased Eln gene expression and altered 126 other matrix-associated genes.
机译：增加的血管刚度与老化成年人心血管并发症的风险较高。如威廉姆斯 - 贝仑综合征或家族性患者患者观察到的ELASTIN（ELN）不足，也增加了血管僵硬并导致动脉缩小。我们使用了eln + /？小鼠测试假设，即病理上增加的血管刚度与伴随的动脉缩小导致血流降低到脑外器官，如脑。我们还假设药物改造动脉和增加腔直径的药物会改善流动。为了测试这些假设，我们使用超声和脑血流使用MRI的动脉旋转标记在野生型（WT）和ELN + /？老鼠。然后我们研究了Minoxidil，ATP敏感K +通道开启器和血管扩张器，影响血管力学，血液流动和基因表达。 Eln + /癌症和脑血流量均较低小鼠比在wt小鼠中。 eln + /何种治疗小鼠含有明辛硅，降低血压并降低官能性动脉刚度至WT水平。米诺西尔还改善了埃恩+ /恢复的颈动脉和脑血流量恢复的颈动脉和脑血流量。老鼠。除药后持续存在的有益效果。 RNA-SEQ分析显示治疗组中127个细胞外基质相关基因的差异表达。这些结果表明，ELN不足损害了终端器官灌注，这可能有助于增加心血管风险。 Minoxidil，尽管血压降低，但改善了末端器官灌注。药物戒断后基因基因表达及治疗效果持续性的变化表明动脉重塑。这种重塑可能有利于遗传或年龄依赖的eln缺陷的患者。新的和值得注意的是我们与慢性血管僵硬模型，弹性蛋白（eln）+ /？通过颈动脉超声和MRI动脉旋转标记测量，鼠标显示出降低的脑灌注。血管口径，功能刚度和血液流动改善了Minoxidil。 ATP敏感K +通道开启器增加了ELN基因表达，并改变了126个其他基质相关基因。

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