Dual role of matrix metalloproteinases-2 in thoracic aortic aneurysm Open Access

[摘要] With matrix metalloproteinases-2 (MMP2) deficiency, we observed thoracic aortic aneurysm in 70% of MMP2-/- mice but no abdominal aortic aneurysm following four weeks of angiotensin II (Ang II) infusion. We found markedly suppressed recoil properties in the thoracic aorta of MMP2-/-- Ang II mice. mRNA and protein levels of elastin, but not collagen, were significantly reduced in the thoracic aorta of MMP2-/--Ang II compared to WT-Ang II mice. This reduction in elastin levels was due to significantly reduced TGFβ-Smad signaling pathway that mediates synthesis of extracellular components. Thus, the adverse remodeling in the thoracic aorta of MMP2-deficient mice was associated with decreased synthesis of extracellular matrix proteins without concomitant upregulation of proteolytic activities. These findings suggest a protective role of MMP2 in the development and progression of aortic aneurysm, and as such inhibition of MMP2 may exacerbate vascular remodeling and lead to development of thoracic aortic aneurysm.

[发布机构] University of Alberta

[效力级别] Aortic aneurysm