Abstract 18971: Effect of Gender on Metalloproteinases/Tissue Inhibitors Expression, Collagen/Elastin Content, and the Mechanical Properties of Ascending Thoracic Aortic Aneurysms
Aim: A greater proportion of female over male patients with ruptured ascending thoracic aortic aneurysms (ATAA) has been documented by epidemiological studies. Our hypothesis was that gender differences in the expression of metalloproteinases MMP-2 and MMP-9, and their endogenous tissue inhibitors TIMP-1 and TIMP-2 may be at the root of the negative outcomes for females, irrespective of aortic and body size. Our study confirmed this hypothesis, determining also the effect of gender on collagen/elastin contents and the mechanical properties of wall tissue.
Methods: One hundred and twenty aortic specimens were resected from the ATAA wall of 30 patients (age: 65±4 years, male/female: 17/13, ATAA diameter: 5.8±0.3 cm), undergoing elective surgery for degenerative ATAA, and categorized by gender: male (n=72) vs. female (n=48). MMP-2, MMP-9, TIMP-1, and TIMP-2 expression was detected immunohistochemically and collagen/elastin content via quantitative histology. Mechanical testing of the vessel wall up to rupture was conducted with a tensile tester, defining tissue strength and maximum stiffness.
Results: Age and ATAA diameter did not differ with gender. An increase in MMP-2 (30.0±1.2 vs. 18.3±0.9%, p<0.001) and MMP-9 (27.4±0.8 vs. 21.4±0.5%, p<0.001) expression was found in females, while TIMP-1 (16.9±0.6 vs. 20.8±0.8%, p<0.001) and TIMP-2 (19.6±0.7 vs. 22.1±0.5%, p<0.05) expression decreased. Collagen (24.1±1.4 vs. 29.3±2.2%, p<0.05) and elastin (12.3±0.5 vs. 19.4±0.9%, p<0.05) contents were lower in females, as were tissue strength (152.9±12.4 vs. 191.0±14.3 N/cm2, p<0.05) and stiffness (825.1±73.2 vs. 1207.4±104.4 N/cm2, p<0.05).
Conclusions: The female gender was associated with excessive expression of MMPs and suppressed expression of TIMPs, eliciting extensive extracellular matrix degradation, as witnessed by the deficient elastin and collagen contents. These immunohistochemical and histological findings related closely with the impaired strength and stiffness in females that may have detrimental consequences for the structural integrity of aortic wall. The present data may further our appreciation of the pathophysiological mechanisms responsible for the higher rupture risk of ATAA in females.
- © 2010 by American Heart Association, Inc.