Decreased aortic diameter and compliance precedes blood pressure increases in postnatal development of elastin-insufficient mice
Decreased aortic diameter and compliance precedes blood pressure increases in postnatal development of elastin-insufficient mice
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DOI：
10.1152/ajpheart.00119.2011
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发表时间：
2011-07-01
影响因子：
4.8
通讯作者：
Wagenseil, Jessica E.
中科院分区：
文献类型：
--
作者：
Le, Victoria P.;Knutsen, Russell H.;Wagenseil, Jessica E.
Le VP，Knutsen RH，Mecham RP，Wagenseil JE.弹性蛋白不足小鼠出生后血压升高前主动脉直径和顺应性降低。美国生理学杂志心脏循环生理学301：H221-H229，2011年。首次发表于2011年5月2日; doi：10.1152/ajpheart.00119.2011。动脉硬化和血压升高是人类和成年小鼠的特征，由于衰老或遗传疾病导致弹性蛋白水平降低。动脉硬化增加与人类高血压之间有直接联系，但尚不清楚是否首先发生机械性能变化或血压升高。使用基因修饰的小鼠与弹性蛋白单倍不足（Eln（+/-）），我们研究了动脉力学性能和血压之间的时间关系，在整个出生后的发展。我们的研究结果表明，一些机械性能保持不变，无论弹性蛋白量。两种基因型的峰值直径顺应性发生在每个年龄的生理压力附近，其作用是提供最大的脉冲阻尼。应力-应变关系在基因型之间是相似的，并且在每个年龄的收缩压附近变得非线性，这用于限制高压下的扩张。我们的研究结果还表明，一些机械性能受到弹性蛋白水平降低的影响，这些变化发生在血压可测量的变化之前。Eln（+/-）小鼠在离体测试中具有降低的主动脉直径和顺应性，这在出生后第7天是显著的，并且升高的血压直到出生后第14天才是显著的。这种时间关系表明，靶向大动脉以增加直径或顺应性可能是治疗人类高血压的有效方法。
Le VP, Knutsen RH, Mecham RP, Wagenseil JE. Decreased aortic diameter and compliance precedes blood pressure increases in postnatal development of elastin-insufficient mice. Am J Physiol Heart Circ Physiol 301: H221-H229, 2011. First published May 2, 2011; doi:10.1152/ajpheart.00119.2011.-Increased arterial stiffness and blood pressure are characteristic of humans and adult mice with reduced elastin levels caused by aging or genetic disease. Direct associations have been shown between increased arterial stiffness and hypertension in humans, but it is not known whether changes in mechanical properties or increased blood pressure occur first. Using genetically modified mice with elastin haploinsufficiency (Eln(+/-)), we investigated the temporal relationship between arterial mechanical properties and blood pressure throughout postnatal development. Our results show that some mechanical properties are maintained constant regardless of elastin amounts. The peak diameter compliance for both genotypes occurs near the physiologic pressure at each age, which acts to provide maximum pulse dampening. The stress-strain relationships are similar between genotypes and become nonlinear near the systolic pressure for each age, which serves to limit distension under high pressure. Our results also show that some mechanical properties are affected by reduced elastin levels and that these changes occur before measurable changes in blood pressure. Eln(+/-) mice have decreased aortic diameter and compliance in ex vivo tests that are significant by postnatal day 7 and increased blood pressure that is not significant until postnatal day 14. This temporal relationship suggests that targeting large arteries to increase diameter or compliance may be an effective treatment for human hypertension.