The Role Matrix Metalloproteinases in the Production of Aortic Aneurysm.

Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type. This chapter will also focus on MMP protein expression rather than on genetic data which may not necessarily translate to increased MMP protein expression. There are supporting data that certain MMPs are increased in the aortic wall. For TAA, it is most notably MMP-1, -9, -12, and -14 and MMP-2 when a bicuspid aortic valve is present. For AAA, it is MMP-1, -2, -3, -9, -12, and -13. The data are weaker or insufficient for the other MMPs. Several studies of gene polymorphisms support MMP-9 for TAA and MMP-3 for AAA as potentially important factors. The signaling pathways in the aorta that can lead to MMP activation include JNK, JAK/stat, osteopontin, and AMP-activated protein kinase alpha2. Substrates in the human vasculature for MMP-3, MMP-9, or MMP-14 include collagen, elastin, ECM glycoprotein, and proteoglycans. Confirmed and potential substrates for MMPs, maintain aortic size and function so that a reduction in their content relative to other components of the aortic wall may produce a failure to maintain aortic size leading to dilatation and aneurysm formation.

Rabkin SW 《-》

The Effect of Nicotine and Tobacco on Aortic Matrix Metalloproteinases in the Production of Aortic Aneurysm.

Rabkin SW 《-》

Expression of matrix metalloproteinases, their tissue inhibitors, and osteopontin in the wall of thoracic and abdominal aortas with dilatative pathology.

Lesauskaite V ，Epistolato MC ，Castagnini M ，Urbonavicius S ，Tanganelli P ... -  《HUMAN PATHOLOGY》

Inflammatory infiltrates and neovessels are relevant sources of MMPs in abdominal aortic aneurysm wall.

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. 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. 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). Inflammatory infiltrates and invading neovessels are relevant sources of MMPs in the AAA wall and may substantially contribute to aneurysm wall instability.

Reeps C ，Pelisek J ，Seidl S ，Schuster T ，Zimmermann A ，Kuehnl A ，Eckstein HH ... -  《-》

Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction.

Chew DK ，Conte MS ，Khalil RA 《JOURNAL OF VASCULAR SURGERY》