Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.
Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.
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DOI：
10.1161/hypertensionaha.114.04456
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Meininger GA
中科院分区：
文献类型：
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作者：
Sehgel NL;Sun Z;Hong Z;Hunter WC;Hill MA;Vatner DE;Vatner SF;Meininger GA
高血压和衰老都被认为会增加主动脉僵硬度，但它们之间的相互作用尚不完全清楚。大多数先前的研究将主动脉僵硬度的增加归因于细胞外基质蛋白的变化，从而改变了血管壁的机械特性。或者，我们假设高血压血管硬度增加的一个重要组成部分是由于血管平滑肌细胞的机械和粘附特性的变化，并且与细胞外基质相比，衰老会增加血管平滑肌细胞的贡献。因此，我们研究了年轻（16 周）和老年（64 周）自发性高血压大鼠和 Wistar-Kyoto 野生型对照的主动脉僵硬度。与年轻的 Wistar-Kyoto 大鼠相比，年轻自发性高血压大鼠的收缩压和脉压显着升高，并且与年龄匹配的对照组相比，老年自发性高血压大鼠的收缩压和脉压继续升高。与 Wistar-Kyoto 大鼠相比，年轻和老年自发性高血压大鼠的切除主动脉环段均表现出显着更大的弹性模量。从胸主动脉分离血管平滑肌细胞，并通过原子力显微镜测量硬度和对纤连蛋白的粘附。高血压会增加血管平滑肌细胞的硬度和血管平滑肌细胞的粘附力，而且这些增加都会随着年龄的增长而加剧。相比之下，高血压并不影响主动脉胶原蛋白和弹性蛋白的组织学指标，这些指标主要因衰老而改变。这支持了这样的概念，即血管平滑肌细胞的硬度和粘附特性是导致高血压与衰老叠加导致主动脉硬度增加的新机制。
Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most prior studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells compared to the extracellular matrix. Accordingly, we studied aortic stiffness in young (16 wks) and old (64 wks) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats, compared to young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats, compared to age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats vs. Wistar-Kyoto rats. Vascular smooth muscle cells were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. This supports the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.