Inflammatory Infiltrates and Neovessels Are Relevant Sources of MMPs in Abdominal Aortic Aneurysm Wall

Abstract

Objectives: Abdominal aortic aneurysm (AAA) wall is characterized by degradation of extracellular matrix through matrix metalloproteinases (MMPs), chronic inflammatory cell infiltration and extensive neovascularization. So far, MMP expression within AAA wall in association with infiltrates and neovascularization has not yet been studied. Methods: Vessel walls of 15 AAA patients and 8 organ donors were analyzed by immunohistochemistry for expression of various MMPs (MMP-1, -2, -3, -7, -8, -9, -12 and -13) in all cells located within the AAAs and correlated with infiltrates and neovascularization. Results: Luminal endothelial cells (ECs) were positive for MMP-1, -3 and -9, ECs of mature neovessels were furthermore positive for MMP-2. Immature neovessels expressed all MMPs tested except for MMP-13. Aortic medial smooth muscle cells (SMCs) expressed MMP-1, -2, -3 and -9, SMCs of mature neovessels, only MMP-1, -3 and -9. Inflammatory infiltrates expressed all MMPs tested except for MMP-2, macrophages expressed all MMPs. Infiltrates were composed mainly of B cells (58.5 ± 10.9%) and T lymphocytes (26.3 ± 9.5%). Furthermore, significant inverse correlations were found between the amounts of inflammatory cells, neovessels and collagen/elastin content of the aortic vessel wall (r = +0.806/p < 0.001, r = –0.650/p = 0.012, r = –0.63/p < 0.015; respectively). Conclusion: Inflammatory infiltrates and invading neovessels are relevant sources of MMPs in the AAA wall and may substantially contribute to aneurysm wall instability.

18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture

“…The expression of MMP13 is strictly regulated and often limited to situations of rapid remodeling; to conditions of chronic inflammation, such as rheumatoid arthritis; and to tumors. Its overexpression in the AAA wall in association with a predominance of B and T lymphocytes was also described (31). MMP1 and MMP13 may cooperate to degrade the adventitial fibrillar collagens type I and III that provide ultimate tensile strength to the aneurysmal aorta, resulting in a progressive weakening of the wall and finally its rupture.…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…Aneurysm. MMP-1 over-expression within AAA wall has been observed in association with infiltrates and neovascularization (Knox et al, 1997) in luminal endothelial cells (EC), aortic medial smooth muscle cells (SMC) and SMC of mature neovessels (Reeps et al, 2009). …”

IgG4-related Inflammatory Abdominal Aortic Aneurysm, Spectrum of IgG4-related Chronic Periaortitis

“…This difference is caused by vasculitis of the vaso vasorum 45,46) or other factors that destroy vascular structure, such as matrix metalloprotease. 47) The difference between IgG4-related IAAA and IRF may be similar, but clear confirmation is necessary.…”