Early growth response factor‑1 DNA enzyme 1 inhibits the formation of abdominal aortic aneurysm in rats

Abstract

The aim of the present study was to characterize the effects of early growth response factor-1 DNA enzyme (EDRz) in a rat abdominal aortic aneurysm (AAA) model to determine the mechanism by which EDRz inhibits AAA and affects the formation of AAA by regulating the activity of matrix metalloproteinase (MMP)-2 and MMP-9. EDRz was transfected into the abdominal aorta of rats using the jetPRIME transfection reagent following infusion with elastase. Fluorescent microscopy, hematoxylin and eosin staining, ultrastructural analysis, reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemical analysis were performed to characterize the response to EDRz. The EDRz group showed minimal aneurysm formation when compared with the control group, with significantly lower aortic diameter expansion (2.5±0.1 vs. 3.5±0.1 mm; P<0.05). Early growth response factor 1 (Egr-1) mRNA and protein levels were significantly decreased in the EDRz group, as expected. The decrease in Egr-1 was accompanied by decreases in the mRNA and protein levels of MMP-2 and MMP-9 (P<0.05). Transfection of the Egr-1 specific synthetic DNA enzyme EDRz significantly reduced AAA following elastase infusion in rats, at least in part due to the decreased expression of downstream MMP-2 and MMP-9.

Metformin Inhibits Abdominal Aortic Aneurysm Formation through the Activation of the AMPK/mTOR Signaling Pathway

“…Pathophysiological research has primarily focused on changes in the expression of elastin-degrading enzymes in human and experimental AAA, especially MMPs and their respective inhibitors [45]. MMPs provide VSMCs with a suitable extracellular environment for migration; this is a major factor in the development of AAA [46, 47]. MMP-2 and MMP-9, which are major members of the MMP family, have been shown to enhance AAA progression [48].…”

Silencing of long non-coding RNA Sox2ot inhibits oxidative stress and inflammation of vascular smooth muscle cells in abdominal aortic aneurysm via microRNA-145-mediated Egr1 inhibition

“…Additionally, Egr1 induction has been attributed to the chronic vascular inflammation in AAA as well as other inflammatory vascular diseases due to its promoting effect on the expression of inflammation-related genes [ 21 , 27 ]. Intriguingly, due to its regulatory role in cell proliferation and apoptosis [ 27 ], Egr1, has been reported to reduce the expression of cell proliferation-related genes MMP2 and MMP9 [ 16 ]. Egr1 has also been shown to promote the intravascular thrombus formation in vivo , contributing to the thrombogenic pathogenesis in human AAA [ 15 ].…”

“…Nevertheless, the conducive role of Egr1 in thrombogenic and inflammatory reaction has been well established in AAA [ 15 ]. Whilst Egr1, a zinc finger transcription factor and a member of the early gene family, has been indicated to participates in various pathophysiological processes, such as cell proliferation, apoptosis, and inflammatory response [ 16 ]. Though the roles of lncRNA Sox2ot, miR-145-5p and Egr1 in the progression of AAA have been reported respectively, the deeper understanding of the effects of the lncRNA Sox2ot/miR-145/Egr1 signaling axis on AAA remains unclear.…”

Disturbed flow's impact on cellular changes indicative of vascular aneurysm initiation, expansion, and rupture: A pathological and methodological review

“…Elastase, a serine protease enzyme that cleaves elastin peptide bonds (Busch et al, 2016; Savastano et al, 2018) injected into a ligated vessel lumen and incubated for 20‐30 min, degrades elastin, and inhibits Ca2+ inflow for vSMC contraction. Elastase‐weakened vessels exposed to disturbed flow can result in aneurysmal growth (Brinjikji, Ding, et al, 2016; Busch et al, 2016; Rowinska et al, 2014): 80% increased abdominal aorta diameter versus control (S. Wang, Dong, et al, 2018). It is worth noting, arterial degradation stabilizes posttreatment, making elastase the primary culprit behind continual aneurysm growth unlikely, instead continued expansion being driven by disturbed flow (Bi et al, 2015).…”