Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms

Abstract

Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic aneurysm (AAA) tissue, but their precise role and potential interaction remain unclear. Experimental induction of aortic aneurysms in mice genetically deficient in these peptidases could provide new insight into AAA pathogenesis. Mice deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their corresponding wild-type background mice (WT) underwent AAA induction by abluminal application of calcium chloride (CaCl 2 ). No aneurysm formation was observed at 10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the corresponding WT mice showed an average 74% and 52% increase in aortic diameter, respectively. Reinfusion of competent macrophages from the corresponding WT strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and mesenchymal cell MMP-2 are both required and work in concert to produce AAA.

VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms

“…A growing number of reports indicate that proteolytic breakdown of extracellular matrix by MMPs contribute to VSMCs migration 31. Moreover, mice deficient in MMP‐2 are actually resistant to aneurysm formation, indicating that MMP‐2 is a causative factor in the pathogenesis of AAA 17, 32. In line with this concept, in our study, we have seen significantly increased MMP‐2 levels in aneurysmatic tissue from our human and murine model of PPE‐induced AAA.…”

“…Migration into the neointima contributes to the progression of AAA. MMPs, especially MMP‐2, mediate extracellular matrix degradation and enable VSMCs migration 17. H 2 O 2 induces MMP‐2 expression in VSMCs and knockdown of VPO1 attenuates this effect (Figure 3A).…”

Dose-Dependent Bidirectional Effect of Angiotensin IV on Abdominal Aortic Aneurysm via Variable Angiotensin Receptor Stimulation

“…In particular, the expression and activity of MMP-2 and MMP-9 are increased in human AAA, which are crucial to the formation of AAA. 20 In our study, we found that medium-dose Ang IV markedly increased collagen deposition in AAA by suppressing the expression and activity of MMP-2 and MMP-9, thus preserving the vascular integrity in ApoE −/− mice, whereas high-dose Ang IV did not have such a prohibitive effect on MMPs.…”

Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity

“…The near absence of MMP-9 expression following exposure of aortic concavity tissue to WSS proves to be an interesting phenomenon. Animal models have indicated that MMP-2 and MMP-9 work synergistically to promote aneurysm formation [49] and that MMP-9 knockout mice are unable to develop aneurysms even under the presence of increased MMP-2 activity [50] . Therefore, the absence of MMP-9 in fresh tissue and tissue subjected to TAV AA and BAV AA WSS, which prevents the possible downstream pathological effects of MMP-2/MMP-9 synergies, may protect the aortic wall against dilation and aneurysm formation.…”