Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Department of Clinical Data of Parkinson's Disease, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Int J Mol Sci. 2021 Dec 28;23(1):315. doi: 10.3390/ijms23010315.
Perlecan (HSPG2), a basement membrane-type heparan sulfate proteoglycan, has been implicated in the development of aortic tissue. However, its role in the development and maintenance of the aortic wall remains unknown. Perlecan-deficient mice (-Tg: Perl KO) have been found to show a high frequency (15-35%) of aortic dissection (AD). Herein, an analysis of the aortic wall of Perl KO mice revealed that perlecan deficiency caused thinner and partially torn elastic lamina. Compared to the control aortic tissue, perlecan-deficient aortic tissue showed a significant decrease in desmosine content and an increase in soluble tropoelastin levels, implying the presence of immature elastic fibers in Perl KO mice. Furthermore, the reduced expression of the smooth muscle cell contractile proteins actin and myosin in perlecan-deficient aortic tissue may explain the risk of AD. This study showed that a deficiency in perlecan, which is localized along the elastic lamina and at the interface between elastin and fibrillin-1, increased the risk of AD, largely due to the immaturity of extracellular matrix in the aortic tissue. Overall, we proposed a new model of AD that considers the deficiency of extracellular molecule perlecan as a risk factor.
基底膜型硫酸乙酰肝素蛋白聚糖 4（HSPG2），也被称为 perlecan，已被认为与主动脉组织的发育有关。然而，其在主动脉壁的发育和维持中的作用尚不清楚。已发现缺乏 perlecan 的小鼠（-Tg:Perl KO）主动脉夹层（AD）的发生频率较高（15-35%）。在此，对 Perl KO 小鼠的主动脉壁进行分析，结果表明 perlecan 缺乏会导致弹性膜更薄且部分撕裂。与对照主动脉组织相比，缺乏 perlecan 的主动脉组织中的 desmosine 含量显著降低，可溶性原弹性蛋白水平升高，这表明 Perl KO 小鼠中存在不成熟的弹性纤维。此外，缺乏 perlecan 的主动脉组织中平滑肌细胞收缩蛋白肌动蛋白和肌球蛋白的表达减少，可能解释了 AD 的风险。本研究表明，定位于弹性膜和弹性蛋白与原纤维蛋白-1 之间界面的 perlecan 缺乏会增加 AD 的风险，这主要归因于主动脉组织中细胞外基质的不成熟。总之，我们提出了一个新的 AD 模型，将细胞外分子 perlecan 的缺乏视为一个风险因素。
