Abdominal aortic aneurysm (AAA) is characterized by chronic aortic wall inflammation and loss of matrix components. Proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) are thought to be involved in this inflammatory process and, therefore, to play an important role in the pathogenesis of human AAA. TNF-α-converting enzyme (TACE) has recently been purified and cloned as a disintegrin and metalloproteinase that converts TNF-α precursor into its mature form. The aim of the present study was to determine whether TNF-α and TACE were expressed and localized in aortic tissues in human AAA. Infrarenal aortic tissues were obtained from AAA patients (n=19) undergoing elective aneurysm reconstruction and from autopsy cases without cardiovascular disorders as normal controls (n=5). Internal thoracic artery samples were also obtained from patients with coronary artery disease undergoing coronary artery bypass grafting to represent biopsied conduit vessels (n=5). The AAA specimens were taken from the mid-portion of the aneurysm and from the longitudinal transition zone between the non-dilated aorta and the proximal aspect of the aneurysm. TNF-α and TACE mRNA levels were determined by real-time quantitative reverse transcriptase–PCR. Expression levels of both TNF-α mRNA and TACE mRNA were significantly greater in the transition zone than in the mid-portion (both P<0.05). Expression levels of both forms of mRNA were significantly higher in AAA samples than in control aortas or atherosclerotic arteries. There was a significant correlation between the expression of TNF-α mRNA with that of TACE mRNA in AAA (r=0.54, P<0.005). Immunostaining was positive for both TNF-α and TACE in CD68-positive macrophages in the media and adventitia obtained from the transition zone in AAA, whereas neither TNF-α nor TACE was expressed in control vessels. In conclusion, the concomitant activation and localization of TNF-α and TACE in the media and adventitia of the transition zone in human AAA underlines the importance of this system in the pathogenesis of this disorder.

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