Expression gradient of metalloproteinases and their inhibitors from proximal to distal segments of abdominal aortic aneurysm

Abstract

Abdominal aortic aneurysm refers to abnormal, asymmetric distension of the infrarenal aortic wall due to pathological remodelling of the extracellular matrix. The distribution of enzymes remodelling the extracellular matrix and their expression patterns in the affected tissue are largely unknown. The goal of this work was to investigate the expression profiles of 20 selected genes coding for metalloproteinases and their inhibitors in the proximal to the distal direction of the abdominal aortic aneurysm. RNA samples were purified from four lengthwise fragments of aneurysm and border tissue obtained from 29 patients. The quantities of selected mRNAs were determined by real-time PCR to reveal the expression patterns. The genes of interest encode collagenases (MMP1, MMP8, MMP13), gelatinases (MMP2, MMP9), stromelysins (MMP3, MMP7, MMP10, MMP11, MMP12), membrane-type MMPs (MMP14, MMP15, MMP16), tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3, TIMP4), and ADAMTS proteinases (ADAMTS1, ADAMTS8, and ADAMTS13). It was found that MMP, TIMP, and ADAMTS are expressed in all parts of the aneurysm with different patterns. A developed aneurysm has such a disturbed expression of the main participants in extracellular matrix remodelling that it is difficult to infer the causes of the disorder development. MMP12 secreted by macrophages at the onset of inflammation may initiate extracellular matrix remodelling, which, if not controlled, initiates a feedback loop leading to aneurysm formation.

Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in intracranial aneurysms

“…Moreover, previous studies have shown that these genes may involve in vascular inflammation, endothelial dysfunction, oxidative stress, VSMC phenotypic switching, cell apoptosis, etc. Table 4 summarizes the current studies on these 10 genes in vascular pathology [ [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] ].…”

Inhibition of Cyclophilin A-Metalloproteinase-9 Pathway Alleviates the Development of Neuropathic Pain by Promoting Repair of the Blood-Spinal Cord Barrier

“…24 It is reported that MMP9 is activated by CypA in the vascular wall of mice with aortic aneurysm, which further aggravates the damage of the BBB by degrading the capillary basement membrane and tight junction proteins. 25 Pharmacological inhibition of MMP9 in vivo with 2-[[(4-phenoxyphenyl)sulfonyl]methyl]-Thiirane (SB-3CT), which eliminated MMP9 activity and normalized tight junction protein levels. 26 Our findings revealed that protein expressions of CypA and MMP9 in mouse spinal cord at days 3 and 7 postoperatively were significantly higher in the CCI group than those of the sham group.…”

Characteristic of cells isolated from human Abdominal Aortic Aneurysm samples cultured in vitro

“…Infiltration of macrophages is associated with increased activity of matrix metalloproteinases 2 and 9, which lead to degradation of the ECM and weaken the aneurysmal wall [26]. In our recent studies, we have shown elevated expression of genes associated with the inflammation process in AAA, e.g., CD68, IL1R2 [10,27]. Flow cytometry of cells from the EL of AAA showed that these cells are positive for CD90 and anti-fibroblast marker, but their numbers were much lower compared with controls.…”