Cheuk Bernice L Y, Cheng Stephen W K
Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China.
J Surg Res. 2004 May 15;118(2):176-82. doi: 10.1016/S0022-4804(03)00351-2.
Abdominal aortic aneurysm (AAA) is a common aged disease of human aorta with increasing incidence. It is characterized by dramatic vascular remodeling via proteolysis and degradation of matrix proteins. Integrins are important cellular receptors for matrix proteins, which may have an association with pathological remodeling. The present study was undertaken to analyze the expression of integrin subunits in human aneurysmal aortas and with healthy aortic tissues as controls.
The expression of integrin genes in AAA specimens and healthy human aortic tissues was detected by RT-PCR technique. The correlation of variation and distribution of smooth muscle cells (SMCs) and integrin protein expression in the corresponding tissues were studied immunohistochemically.
The gene transcripts coding for integrin alpha4, alpha5, alphaV, beta1, beta3, beta5, and beta6 subunits were constitutively expressed in the normal aortas. Only gene expressions of integrin alpha5 and beta1 were significantly decreased by 81% and 85%, respectively, in AAA specimens (P < 0.005) when compared with healthy aortic specimens. No age dependence of the expression of integrin alpha5beta1 genes was found. Significant reduction of medial SMC density was confirmed in corresponding AAA compared with control aortas. Immunoreactivity of integrin alpha5beta1 receptor was found to be exclusively localized within the medial layer of the parallel normal aortic sections, whereas this protein was absent in the destructive media of aneurysmal aortic sections.
The marked decrease in integrin alpha5beta1 expressions was unique to aneurysmal aortic tissues and correlated to a decrease in density of SMCs, which are the major cells in maintaining the structure stability of normal aortas. As integrin alpha5beta1 specifically binds fibronectin and collagen, those results may suggest that the absence of integrin alpha5beta1 activity impair matrix protein attachment and alter the architecture in aortic media thereby lead to the deformity of aorta and aneurysm formation.
腹主动脉瘤（AAA）是一种常见的人类主动脉老年疾病，发病率呈上升趋势。其特征是通过基质蛋白的蛋白水解和降解进行显著的血管重塑。整合素是基质蛋白的重要细胞受体，可能与病理重塑有关。本研究旨在分析整合素亚基在人类动脉瘤主动脉中的表达，并以健康主动脉组织作为对照。
采用逆转录聚合酶链反应（RT-PCR）技术检测AAA标本和健康人主动脉组织中整合素基因的表达。通过免疫组织化学研究相应组织中平滑肌细胞（SMC）的变异和分布与整合素蛋白表达的相关性。
编码整合素α4、α5、αV、β1、β3、β5和β6亚基的基因转录本在正常主动脉中组成性表达。与健康主动脉标本相比，AAA标本中仅整合素α5和β1的基因表达分别显著降低了81%和85%（P < 0.005）。未发现整合素α5β1基因表达的年龄依赖性。与对照主动脉相比，相应的AAA中中膜SMC密度显著降低。发现整合素α5β1受体的免疫反应性仅局限于正常主动脉平行切片的中膜层，而在动脉瘤主动脉切片的破坏中膜中则不存在这种蛋白。
整合素α5β1表达的显著降低是动脉瘤主动脉组织所特有的，并且与SMC密度的降低相关，SMC是维持正常主动脉结构稳定性的主要细胞。由于整合素α5β1特异性结合纤连蛋白和胶原蛋白，这些结果可能表明整合素α5β1活性的缺失损害了基质蛋白的附着，并改变了主动脉中膜的结构，从而导致主动脉畸形和动脉瘤形成。
