Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.
Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.
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DOI：
10.1016/j.cjca.2015.11.004
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Milewicz DM
中科院分区：
文献类型：
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作者：
Karimi A;Milewicz DM
主动脉内层赋予主动脉壁弹性和强度，由平滑肌细胞 (SMC) 和弹性纤维的交替层组成。 SMC 弹性蛋白收缩单元是将弹性蛋白纤维连接到 SMC 的结构单元，其特征如下： 1. 被微原纤维包围的弹性蛋白纤维层。 2. 与 SMC 细胞表面粘着斑中的整合素受体结合的微原纤维。 3. SMC 收缩丝，与膜内侧的粘着斑相连。被改变导致胸主动脉瘤和主动脉夹层的基因编码参与 SMC 弹性蛋白（收缩单位）结构或功能的蛋白质。该基因列表中包括编码作为弹性蛋白纤维和微原纤维结构成分的蛋白质、FBN1、MFAP5、ELN 和 FBLN4 的基因。还包括 SMC 收缩单位中的结构蛋白基因，包括编码 SMC 特异性 α-肌动蛋白的 ACTA2 和编码 SMC 特异性肌球蛋白重链的 MYH11，以及编码控制 SMC 收缩的激酶的 MYLK 和 PRKG1。最后，编码将整合素受体与收缩丝连接的蛋白质 FLNA 的基因突变也会导致胸主动脉疾病。因此，这些数据表明功能性 SMC 弹性蛋白收缩单位对于维持主动脉的结构完整性非常重要。
The medial layer of the aorta confers elasticity and strength to the aortic wall and is composed of alternating layers of smooth muscle cells (SMCs) and elastic fibers. The SMC elastin-contractile unit is a structural unit that links the elastin fibers to the SMCs and is characterized by the following: 1. Layers of elastin fibers that are surrounded by microfibrils. 2. Microfibrils that bind to the integrin receptors in focal adhesions on the cell surface of the SMCs. 3. SMC contractile filaments that are linked to the focal adhesions on the inner side of the membrane. The genes that are altered to cause thoracic aortic aneurysms and aortic dissections encode proteins involved in the structure or function of the SMC elastin – contractile unit. Included in this gene list are the genes encoding protein that are structural components of elastin fibers and microfibrils, FBN1, MFAP5, ELN, and FBLN4. Also included are genes that are structural proteins in the SMC contractile unit, including ACTA2, which encodes SMC-specific α-actin and MYH11, which encodes SMC-specific myosin heavy chain, along with MYLK and PRKG1, which encode kinases that control SMC contraction. Finally, mutations in the gene encoding the protein linking integrin receptors to the contractile filaments, FLNA, also cause thoracic aortic disease. Thus, these data suggest that functional SMC elastin-contractile units are important for maintaining the structural integrity of the aorta.