Differential expression of integrin α5β1 in human abdominal aortic aneurysm and healthy aortic tissues and its significance in pathogenesis

Abstract

Background 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. Materials and methods 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. Results The gene transcripts coding for integrin α4, α5, αV, β1, β3, β5, and β6 subunits were constitutively expressed in the normal aortas. Only gene expressions of integrin α5 and β1 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 α5β1 genes was found. Significant reduction of medial SMC density was confirmed in corresponding AAA compared with control aortas. Immunoreactivity of integrin α5β1 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. Conclusions The marked decrease in integrin α5β1 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 α5β1 specifically binds fibronectin and collagen, those results may suggest that the absence of integrin α5β1 activity impair matrix protein attachment and alter the architecture in aortic media thereby lead to the deformity of aorta and aneurysm formation. © 2004 Elsevier Inc. All rights reserved.