Effects of elastin haploinsufficiency on the mechanical behavior of mouse arteries
Effects of elastin haploinsufficiency on the mechanical behavior of mouse arteries
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DOI：
10.1152/ajpheart.00046.2005
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发表时间：
2005-09-01
影响因子：
4.8
通讯作者：
Mecham, RP
中科院分区：
文献类型：
--
作者：
Wagenseil, JE;Nerurkar, NL;Mecham, RP
主动脉瓣上狭窄（SVAS）与弹性蛋白减少和动脉力学改变有关。在弹性蛋白基因中具有单个缺失（ELN+/-）的小鼠是SVAS的模型。先前的研究表明，这些小鼠中的弹性蛋白单倍不足导致高血压、动脉顺应性降低和动脉壁结构变化。尽管存在这些差异，ELN+/-小鼠具有正常的寿命，这表明动脉重塑并适应弹性蛋白量的减少。为了验证这一假设，我们对ELN+/-和野生型（C57 BL/6 J）小鼠的腹主动脉、升主动脉和左颈总动脉进行了体外力学测试。我们比较了周向和纵向的应力-拉伸关系和残余应变。周向应力-拉伸关系在基因型之间是相似的，并且在长度在体内值的10%内的纵向拉伸下变化< 3%。在平均动脉压下，ELN+/-中升主动脉的周向应力高于野生型。尽管动脉压较高，但ELN+/-动脉中弹性膜数量的增加导致与野生型相似的张力/弹性膜。大多数动脉的纵向应力-拉伸关系在基因型之间是相似的。与野生型相比，ELN+/-腹动脉和颈动脉的体内纵向拉伸较低，ELN+/-升主动脉的周向残余应变较高。增加的周向残余应变使ELN+/-升主动脉的跨壁应变分布接近野生型值。ELN+/-动脉的机械行为可能是由于血管发育过程中弹性蛋白含量减少以及适应性重塑。
Supravalvular aortic stenosis (SVAS) is associated with decreased elastin and altered arterial mechanics. Mice with a single deletion in the elastin gene (ELN+/-) are models for SVAS. Previous studies have shown that elastin haploinsufficiency in these mice causes hypertension, decreased arterial compliance, and changes in arterial wall structure. Despite these differences, ELN+/- mice have a normal life span, suggesting that the arteries remodel and adapt to the decreased amount of elastin. To test this hypothesis, we performed in vitro mechanical tests on abdominal aorta, ascending aorta, and left common carotid artery from ELN+/- and wild-type (C57BL/6J) mice. We compared the circumferential and longitudinal stress-stretch relationships and residual strains. The circumferential stress-stretch relationship is similar between genotypes and changes < 3% with longitudinal stretch at lengths within 10% of the in vivo value. At mean arterial pressure, the circumferential stress in the ascending aorta is higher in ELN+/- than in wild type. Although arterial pressures are higher, the increased number of elastic lamellae in ELN+/- arteries results in similar tension/lamellae compared with wild type. The longitudinal stress-stretch relationship is similar between genotypes for most arteries. Compared with wild type, the in vivo longitudinal stretch is lower in ELN+/- abdominal and carotid arteries and the circumferential residual strain is higher in ELN+/- ascending aorta. The increased circumferential residual strain brings the transmural strain distribution in ELN+/- ascending aorta close to wild-type values. The mechanical behavior of ELN+/- arteries is likely due to the reduced elastin content combined with adaptive remodeling during vascular development.