Dexmedetomidine suppresses the development of abdominal aortic aneurysm by downregulating the mircoRNA‑21/PDCD 4 axis

Abstract

Abdominal aortic aneurysm (AAA) is a pathological state with permanent dilation, which indicates a fatal potential for aortic rupture. It has been reported that dexmedetomidine (dex) and microRNA (miR)-21 are involved in the progression of AAA. Thus, the present study aimed to investigate the joint effects of these factors on AAA treatment. For this purpose, rat models of AAA were established with enzyme perfusion and the rats were then injected with dex. Alterations in the abdominal aorta in rats with AAA were recorded. miR-21 expression in the rats with AAA was determined. Inflammatory factor expression was detected by western blot analysis. Subsequently, a dual-luciferase reporter gene assay was performed to verify the targeting association between miR-21 and programmed cell death protein 4 (Pdcd4). Additionally, AAA-related indices and inflammatory responses were examined by an injection of a combination of antagomiR (ant)-miR-21 and dex or lentivirus-Pdcd4-short hairpin RNA. It was found that dex markedly alleviated the development of AAA and downregulated the expression of inflammatory factors and matrix metalloproteinase in rats with AAA. The high expression of miR-21, which targets Pdcd4, was observed in the rats with AAA. However, ant-miR-21 induced AAA development and inflammatory responses. Additionally, the inhibition of Pdcd4 reduced AAA development and inflammatory responses. On the whole, the present study demonstrates that dex inhibits AAA development by downregulating the miR-21/PCDP4 axis. The findings of the present study may provide novel insight for the treatment of AAA. These findings may provide a reference for the future treatment of AAA and may provide theoretical guidance for the early prevention and development of AAA.

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

“…Successful induction was defined as the appearance of hemiplegia 24 h after MCAO. Rats were euthanized by an injection of excessive sodium pentobarbital (800 mg/kg) ( 40 ); successful euthanasia was defined as the disappearance of reflex and respiration, and cardiac arrest. Following euthanasia, the brain tissues of 6 rats from each group were randomly selected for triphenyltetrazolium chloride (TTC) staining, and those from the other 10 rats were collected for follow-up biochemical tests.…”

Dexmedetomidine represses TGF-β1-induced extracellular matrix production and proliferation of airway smooth muscle cells by inhibiting MAPK signaling pathway

“…25 The proliferative effect of TGF-β1 on ASMCs was first ascertained in this study as demonstrated by increased cell viability and proliferation of ASMCs after TGF-β1 treatment, and TGF-β1-repressed cell apoptosis of ASMCs. Dexmedetomidine has been reported to enhance expression of miR-21 and reduce expression of programmed cell death protein 4 to repress the development of abdominal aortic aneurysm, 26 and TGF-β1 up-regulated miR-181a to decrease phosphatase and tensin homologue deleted on chromosome ten (PTEN) in asthmatic mice. 27 Therefore, dexmedetomidine might regulate miR-181a/PTEN to be implicated in the TGF-β1-induced ECM production and proliferation of ASMCs.…”

Bioinformatics-based identification of lipid- and immune-related biomarkers in abdominal aortic aneurysms

“…All SD rats were randomly divided into sham and AAA groups, with 6 animals in each group. AAA animal models were constructed as described previously [ 19 , 20 ]. In brief, SD rats in the AAA group were anesthetized with 2.5% gaseous isoflurane and subjected to systemic heparinization.…”