Functional limitations due to axial and peripheral joint impairments in patients with ankylosing spondylitis: are focused measures more informative?

OBJECTIVE: Functional limitations in ankylosing spondylitis (AS) may be due to peripheral joint or axial involvement. To determine if the Bath Ankylosing Spondylitis Functional Index (BASFI), an axial-focused measure, can detect limitations related to peripheral joint involvement equally as well as the Health Assessment Questionnaire modified for the spondyloarthropathies (HAQ-S), a peripheral arthritis-focused measure, and vice versa, we compared associations of each questionnaire with spinal and hip range of motion, peripheral arthritis, and enthesitis in patients with AS. METHODS: We examined patients every 4-6 months in this prospective longitudinal study. We used mixed linear models to analyze the associations between 10 physical examination measures and the BASFI and HAQ-S. RESULTS: We studied 411 patients for a median of 1.5 years (median 3 visits). In multivariate analyses, cervical rotation, chest expansion, lateral thoracolumbar flexion, hip motion, tender joint count, and tender enthesis count were equally strongly associated with the BASFI and HAQ-S. Peripheral joint swelling was more strongly associated with the HAQ-S. Individual items of the BASFI were more likely than items of the HAQ-S to be associated with unrelated physical examination measures (e.g., the association between difficulty rising from a chair and cervical rotation), which may have diminished the axial/peripheral distinction for the BASFI. CONCLUSION: The BASFI and HAQ-S had similar associations with impairments in axial measures, while the HAQ-S had stronger associations with the number of swollen peripheral joints. The HAQ-S should be considered for use in studies focused on spondyloarthritis with peripheral joint involvement.

A biologic basis for asymmetric growth in descending thoracic aortic aneurysms: a role for matrix metalloproteinase 9 and 2.

OBJECTIVE: This study was undertaken to define matrix metalloproteinase (MMP) expression in the anterior and posterior wall of descending thoracic aortic aneurysms (TAAs) and correlate it with specific computed tomography (CT) image sites within the descending thoracic aorta. METHODS: Serial CT images of patients with TAAs were compared with age- and gender-matched normal descending thoracic aortas at levels T4-T12. The mean circumference of the TAAs was 153 mm (n = 12) and 148 mm (n = 11) at T8 and T10, respectively, compared with 75 mm (n = 12) and 75 mm (n = 10) in controls (P < .001). Aortic tissue was collected from a separate set of eight patients undergoing descending TAA resection (processed < or =12 hours of excision) and six cadavers (processed < or =24 hours of death). Tissue collected between the intercostals arteries was defined as posterior wall, and directly opposite was the anterior wall. MMP-9 and MMP-2 messenger RNA (mRNA) extracted from aortic tissue was analyzed by quantitative real time polymerase chain reaction (PCR) and normalized to beta-actin. Immunohistochemistry was performed for MMP-9 and MMP-2. CT aortic measurements and MMP expression were compared by t tests and analysis of variance, respectively. RESULTS: The ratio of arc distance between the intercostals on the posterior wall to total aortic circumference was 0.14 in healthy controls compared with 0.08 in TAAs at vertebral level T8 (P = .001). At T10, the ratio was 0.15 in healthy controls compared with 0.11 in TAAs (P = .001). MMP-9 expression in TAAs was 4.3-fold higher in the anterior wall compared with the posterior wall (P = .03). Conversely, MMP-2 expression in TAAs was 3.2-fold higher in the posterior wall compared with the anterior wall (P = .008). MMP expression was not detected in control cadaver aortas. CONCLUSION: Anterior walls of expanding TAAs grow at a greater rate than the posterior wall, as determined from the lower ratio of intercostal arc distance to total circumference in TAAs. Differential MMP expression appears to be a biologic marker for asymmetric growth in the TAA wall. CLINICAL RELEVANCE: The pathogenesis of thoracic aortic aneurysms (TAAs) is poorly understood. Multiple lines of evidence suggest that matrix metalloproteinases (MMPs), a family of enzymes, are important in aneurysm development. Earlier experiments documented a regional variation of MMP-9 in stimulated rodent aortas, with production greater in the abdominal aorta compared with the thoracic aorta. The present study extends that observation and documents asymmetric aneurysm development in the TAA wall, with increased anterior wall growth in correlation to increased MMP-9 production. An improved understanding of the mechanisms by which MMP production is regulated is critical.

Early MT-1 MMP expression following elastase exposure is associated with increased cleaved MMP-2 activity in experimental rodent aortic aneurysms.

OBJECTIVE: The objective of this study was to determine the significance of membrane type 1 matrix metalloproteinase (MT1-MMP) activation of MMP-2 in experimental abdominal aortic aneurysms. METHODS: Rat aortas were perfused with either saline as a control or elastase, and harvested on 2, 4, or 7 days after perfusion (n = 5 per treatment group/day). Aortic MT1-MMP and MMP-2 expression and protein were determined by real time polymerase chain reaction and Western blotting, respectively. Aortic explants were used to measure MMP-2 activity by zymography. Rat aortic smooth muscle cells in vitro were exposed to increasing doses of elastase and analyzed for MT-1 MMP expression. RESULTS: Aneurysms formed in 80% of the elastase-perfused aortas at 7 days, whereas none formed in the saline-perfused aortas. Significantly increased MT1-MMP expression was observed only on day 4, when levels were 6.5-fold higher in elastase-perfused aortas compared with saline-perfused aortas (P < .01). By day 7, MT1-MMP protein was present only in the elastase-perfused aortas (P = .02). By immunohistochemistry, MT1-MMP was detectable only in the elastase-perfused group at day 7. Cleaved MMP-2 activity (P = .045) was increased in elastase-perfused aortas compared with saline perfused aortas at day 7. In rat aortic smooth muscle cells, MT-1 MMP expression increased in response to elastase (P = .02). CONCLUSION: The rodent aortic aneurysm model exhibits upregulation of MT1-MMP expression and protein with subsequent increased conversion of MMP-2 from the latent to the cleaved form.