Differential expression of integrin alpha5beta1 in human abdominal aortic aneurysm and healthy aortic tissues and its significance in pathogenesis.
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.


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 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.


CONCLUSIONS
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.
Cheuk
Bernice L Y
BL
Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China.
Cheng
Stephen W K
SW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000378:metabolism / Q000502:physiology*; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D039081:Integrin alpha5beta1 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D039081:Integrin alpha5beta1; D012333:RNA, Messenger