Dye W W, Gleason R L, Wilson E, Humphrey J D
Dept. of Biomedical Engineering, M. E. DeBakey Institute, Texas A&M University, College Station, TX 77843-3120, USA.
J Appl Physiol (1985). 2007 Aug;103(2):664-72. doi: 10.1152/japplphysiol.00118.2007. Epub 2007 May 24.
Muscular dystrophy is characterized by skeletal muscle weakness and wasting, but little is known about possible alterations to the vasculature. Many muscular dystrophies are caused by a defective dystrophin-glycoprotein complex (DGC), which plays an important role in mechanotransduction and maintenance of structural integrity in muscle cells. The DGC is a group of membrane-associated proteins, including dystrophin and sarcoglycan-delta, that helps connect the cytoskeleton of muscle cells to the extracellular matrix. In this paper, mice lacking genes encoding dystrophin (mdx) or sarcoglycan-delta (sgcd-/-) were studied to detect possible alterations to vascular wall mechanics. Pressure-diameter and axial force-length tests were performed on common carotid arteries from mdx, sgcd-/-, and wild-type mice in active (basal) and passive smooth muscle states, and functional responses to three vasoactive compounds were determined at constant pressure and length. Apparent biomechanical differences included the following: mdx and sgcd-/- arteries had decreased distensibilities in pressure-diameter tests, with mdx arteries exhibiting elevated circumferential stresses, and mdx and sgcd-/- arteries generated elevated axial loads and stresses in axial force-length tests. Interestingly, however, mdx and sgcd-/- arteries also had significantly lower in vivo axial stretches than did the wild type. Accounting for this possible adaptation largely eliminated the apparent differences in circumferential and axial stiffness, thus suggesting that loss of DGC proteins may induce adaptive biomechanical changes that can maintain overall wall mechanics in response to normal loads. Nevertheless, there remains a need to understand better possible vascular adaptations in response to sustained altered loads in patients with muscular dystrophy.
肌肉萎缩症的特征是骨骼肌无力和萎缩，但对于其脉管系统可能存在的改变却知之甚少。许多肌肉萎缩症是由肌营养不良蛋白-糖蛋白复合物（DGC）缺陷引起的，该复合物在肌肉细胞的机械转导和结构完整性维持中起重要作用。DGC是一组与膜相关的蛋白质，包括肌营养不良蛋白和δ-肌聚糖，它有助于将肌肉细胞的细胞骨架与细胞外基质连接起来。在本文中，研究了缺乏编码肌营养不良蛋白（mdx）或δ-肌聚糖（sgcd-/-）基因的小鼠，以检测血管壁力学可能存在的改变。对mdx、sgcd-/-和野生型小鼠的颈总动脉在主动（基础）和被动平滑肌状态下进行压力-直径和轴向力-长度测试，并在恒定压力和长度下测定对三种血管活性化合物的功能反应。明显的生物力学差异包括：在压力-直径测试中，mdx和sgcd-/-动脉的扩张性降低，mdx动脉的周向应力升高，并且在轴向力-长度测试中，mdx和sgcd-/-动脉产生的轴向负荷和应力升高。然而，有趣的是，mdx和sgcd-/-动脉在体内的轴向伸展也明显低于野生型。考虑到这种可能的适应性变化在很大程度上消除了周向和轴向刚度的明显差异，这表明DGC蛋白的缺失可能会诱导适应性生物力学变化，从而在正常负荷下维持整体血管壁力学。尽管如此，仍有必要更好地了解肌肉萎缩症患者在持续改变的负荷下可能出现的血管适应性变化。
