弹性蛋白收缩单元在胸主动脉夹层发病机制中的研究进展

Current advances in the mechanism of elastin-contractile units in the pathogenesis of thoracic aortic dissection

主动脉壁的中膜层由平滑肌细胞(smooth muscle cell,SMC)和弹性纤维交替组成,其对于主动脉弹性和强度至关重要。中膜SMC中的弹性蛋白收缩单元起着连接细胞外的弹性纤维和细胞内的收缩骨架的作用。此弹性收缩单元中的编码结构或者功能蛋白的基因发生突变会导致胸主动脉瘤或夹层。其中编码弹性蛋白纤维和弹性微纤维的基因有FBN1、MFAP5、ELN、FBLN4;编码弹性蛋白收缩单元的基因有ACTA2和MYH11。ACTA2基因编码平滑肌特异的α肌动蛋白;MYH11基因编码SMC特异肌球蛋白重链;而MYLK与PRKG1一起共同编码控制SMC收缩的激酶;FLNA基因编码连接收缩丝和整合素受体的蛋白质,当这些相关基因发生突变时,都将增加发生胸主动脉疾病的倾向性。综上,功能性SMC弹性蛋白收缩单元对于维持主动脉结构的完整性有着重要作用。

The tunica media of aortic wall is composed of smooth muscle cell （SMC） and elastic fibers, which determine the elasticity and rigidity of aorta. In the middle layer, the elastin-contractile units play an important role in connecting the elastic fibers and the cytoskeleton. The mutation of gene that coding structure or functional protein in the elastin-contractile units can lead to thoracic aortic aneurysm or dissection. Among them, FBN1 and MFAP5, ELN, and FBLN4 were the genes encoding elastin fibers and elastic microfibrils. The genes encoding the composite of elastin-contractile units were ACTA2 and MYH11. Also included are genes that encode structural proteins in the SMC contractile unit： the ACTA2 gene encoding smooth muscle alpha actin specific; MYH11 gene encoding SMC specific myosin heavy chain; MYLK together with PRKG1 to control SMC encoding contraction kinase; FLNA gene encoding integrin receptor connected shrinkage filament protein. One or more of these genes mutated that related to sudden change, will increase the tendency of thoracic aortic diseases. In summary, the function of SMC elastin-contractile units plays an important role in maintaining the integrity of the aortic structure.