We hypothesized that female gender may have a specific negative impact on the mechanical
characteristics, composition, and expression of matrix metalloproteinases/tissue inhibitors
(MMPs/TIMPs) in the wall of ascending thoracic aortic aneurysms (ATAAs). Degenerative
ATAAs were resected from 35 patients (age: 67±2 years, male: 20, ATAA diameter: 5.5±0.1cm)
undergoing elective surgery. Tissue specimens were grouped by gender, region, and
direction and submitted to immunohistochemistry for semi-quantitative assessment of
MMP-2, MMP-9, TIMP-1, and TIMP-2 expressions, i.e. of staining intensity in extracellular
matrix and immunoreactivity in vascular cells, as well as to histology for quantitation
of elastin/collagen contents. Biomechanical characterization by the Fung-type model
and examination of failure properties was performed. Gender differences in patient
age, ATAA diameter, and ATAA diameter/body-surface area were non-significant. Increased
MMP-2 and MMP-9, and decreased TIMP-1 and TIMP-2 expressions were observed in females.
Elastin/collagen contents were higher in males than females, as was failure stress
in circumferential but not longitudinal specimens. In both directions, failure stretch
was invariant, while the Fung-type model parameters and elastic moduli calculated
at physiologic stress levels were higher in females, suggestive of increased wall
stiffness compared to males. MMP and TIMP expressions did not differ with region,
unlike failure stress longitudinally that was greater posteriorly than anteriorly.
The female gender is associated with impaired ATAA strength and increased stiffness,
relating to the more extensive extracellular matrix breakdown and significantly higher
ratio of MMP/TIMP expression witnessed in females. The present data may aid to identify
the underlying pathophysiology accountable for the higher rupture risk, documented
by epidemiologic studies in females.