Matrix metalloproteinases in aortic dissection.

Aortic dissection, characterized by a high immediate mortality, is primarily caused by excessive bleeding within the walls of the aorta or a severe tear within the intimal layer of the aorta. Inflammation, as well as oxidative stress and the degradation of extracellular matrix (ECM), are significant factors in the development and occurrence of aortic dissection. Matrix metalloproteinases (MMPs) are pivotal enzymes responsible for degrading the ECM. Inflammatory factors and oxidants can interact with MMPs, indicating the potential significance of MMPs in aortic dissection. A substantial body of evidence indicates that numerous MMPs are significantly upregulated in aortic dissection, playing a critical role in ECM degradation and the pathogenesis of aortic dissection. Furthermore, targeting these enzymes has demonstrated potential in facilitating ECM restoration and reducing the incidence of aortic dissection. This review initially provides a brief overview of MMP biology before delving into their expression patterns, regulatory mechanisms, and therapeutic applications in aortic dissection. A profound comprehension of the catabolic pathways associated with aortic dissection is imperative for the future development of potential preventive or therapeutic bio-interventions for aortic dissection.

Zhou S ，Ma B ，Luo M 《-》

Thoracic aortic dissection: are matrix metalloproteinases involved?

Zhang X ，Shen YH ，LeMaire SA 《-》

Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection.

Akiyama M ，Ohtani H ，Sato E ，Nagura H ，Tabayashi K ... -  《VIRCHOWS ARCHIV》

Matrix metalloproteinase levels in chronic thoracic aortic dissection.

Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can lead to aortic wall failure. We hypothesized that patients with aneurysms resulting from chronic descending thoracic aortic dissection have elevated tissue and plasma levels of specific MMPs and decreased tissue levels of TIMPs. Aortic tissue was obtained from 25 patients who required surgical repair of descending thoracic aortic aneurysm due to chronic aortic dissection and from 17 organ-donor controls without aortic disease. Tissue levels of MMP-1, -2, -3, -9, -12, and -13 and TIMP-1 and -2 were measured by colorimetric activity assay or enzyme-linked immunosorbent assay and confirmed by Western blot and immunohistochemistry. Blood obtained from the 25 patients and 15 controls without aortic diseases was used to compare plasma levels of MMP-3, -9, and -12. Total MMP-1, total MMP-9, and active MMP-9 levels were higher and total MMP-2 levels were lower in dissection tissue than in control tissue. Additionally, the MMP-9 to TIMP-1 and active to total MMP-2 ratios were higher and the MMP-2 to TIMP-2 ratio was lower in dissection tissue. Furthermore, patients had higher plasma active to total MMP-9 ratios than the controls. Age and hypertension were associated with increased MMP levels. Increased levels of several MMPs and increased MMP to TIMP ratios in aortic tissue from patients suggest an environment that favors proteolysis, which may promote progressive extracellular matrix destruction and medial degeneration after aortic dissection. An elevated active to total MMP-9 ratio in plasma may be a biomarker for end-stage aneurysm development in patients with chronic thoracic aortic disease.

Zhang X ，Wu D ，Choi JC ，Minard CG ，Hou X ，Coselli JS ，Shen YH ，LeMaire SA ... -  《-》

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 《-》