scholarly journals MiR-143 Mediates the TLR2/NF-κB Pathway to Attenuate AngII-induced Damage to VSMCs

2021 ◽  
Vol 69 (2) ◽  
pp. 81-92
Author(s):  
Zhenhua Wang ◽  
Feng Lin ◽  
Zhaoling Cai ◽  
Guorong Lyu

Abdominal aortic aneurysm (AAA) is a perilous vascular disease with inflammatory response as its main feature. It is known that the expression of miR-143 is down-regulated in the human aortic aneurysm. In this study, we investigated the effect of miR-143 on AngII-induced VSMCs to learn the potential mechanisms of miR-143 on AAA at the cellular level. The experimental results showed that the expressions of IL-1β, MCP-1, MMP9/13, TLR2, and NF-κB p65 and the percentage of TUNEL-positive cells in AngII-VSMCs were increased significantly compared with the control group. miR-143 had the opposite result. When the expression of miR-143 was up-regulated, the expression of IL-β, MCP-1, and MMP9/13 and the percentage of TUNEL-positive cells in AngII-VSMCs was suppressed. With the transfection of miR-143 over-expression plasmid, IL-1β, MCP-1, and MMP9/13 and the percentage of TUNEL-positive cells were reversed, compared to the AngII group and the AngII+oe-TLR2+miR-143 mimic group. In AngII-induced mouse VSMC, the up-regulation of the miR-143 expression could inactivate the TLR2/NF-κB pathway, thereby alleviating inflammatory response, ECM degradation, and cell apoptosis.

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Abulaihaiti Maitiseyiti ◽  
Hongbo Ci ◽  
Qingbo Fang ◽  
Sheng Guan ◽  
Alimujiang Shawuti ◽  
...  

Objective. Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various diseases. However, the potential regulatory role of lncRNAs in the pathogenesis of abdominal aortic aneurysm (AAA) remains elusive. The aim of this study was to identify crucial lncRNAs associated with human AAA by comparing the lncRNA and mRNA expression profiles of patients with AAA with those of control individuals. Materials and Methods. The expression profiles of lncRNAs and mRNAs were analyzed in five dilated aortic samples from AAA patients and three normal aortic samples from control individuals using microarray technology. Functional annotation of the screened lncRNAs based on the differentially expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results. Microarray results revealed 2046 lncRNAs and 1363 mRNAs. Functional enrichment analysis showed that the mRNAs significantly associated with AAA were enriched in the NOD-like receptor (NLR) and nuclear factor kappa-B (NF-κB) signaling pathways and in cell adhesion molecules (CAMs), which are closely associated with pathophysiological changes in AAA. The lncRNAs identified using microarray analysis were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis with 12 versus 11 aortic samples. Finally, three key lncRNAs (ENST00000566954, ENST00000580897, and T181556) were confirmed using strict validation. A coding-noncoding coexpression (CNC) network and a competing endogenous RNA (ceRNA) network were constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs. Conclusions. Our microarray profiling analysis and validation of significantly expressed lncRNAs between patients with AAA and control group individuals may provide new diagnostic biomarkers for AAA. The underlying regulatory mechanisms of the confirmed lncRNAs in AAA pathogenesis need to be determined using in vitro and in vivo experiments.


2019 ◽  
Vol 7 ◽  
pp. 205031211983350 ◽  
Author(s):  
Kristian Smidfelt ◽  
Joakim Nordanstig ◽  
Urban Wingren ◽  
Göran Bergström ◽  
Marcus Langenskiöld

Objective: To investigate whether a strategy of treatment with a primarily open abdomen improves outcome in terms of mortality and major complications in patients treated with open repair for a ruptured abdominal aortic aneurysm compared to a strategy of primary closure of the abdomen. Design: Retrospective cohort study. Methods: Patients treated with a primarily open abdomen at a centre where this strategy was routine in most ruptured abdominal aortic aneurysm patients were compared to a propensity score–matched control group of patients who had the abdomen closed at the end of the primary operation in a majority of the cases. Results: In total, 79 patients treated with a primarily open abdomen after open repair for ruptured abdominal aortic aneurysm at Sahlgrenska University Hospital were compared to a propensity score–matched control group of 148 patients. The abdomen was closed at the end of the procedure in 108 (73%) of the control patients. There was no difference in 30-day mortality between patients treated with a primarily open abdomen at Sahlgrenska University Hospital and the controls, 21 (26.6%) versus 49 (33.1%), p = 0.37. The adjusted odds ratio for mortality at 30 days was 0.66 (95% confidence interval: 0.35–1.25) in patients treated with a primarily open abdomen at Sahlgrenska University Hospital compared to the controls. No difference was observed between the groups regarding 90-day mortality, postoperative renal failure requiring renal replacement therapy, postoperative intestinal ischaemia necessitating bowel resection or postoperative bleeding requiring reoperation. Conclusions: The study did not show any survival advantage or difference in major complications between patients treated with a primarily open abdomen after open repair for ruptured abdominal aortic aneurysm and propensity-matched controls where the abdomen was primarily closed in a majority of the cases.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
QingQing Hao ◽  
Xu Chen ◽  
XiaoYu Wang ◽  
Bo Dong ◽  
ChuanHua Yang

Background and Objectives. Curcumin has long been used to treat age-related diseases, such as atherosclerosis and coronary heart disease. In this study, we explored the effects of curcumin on the development of abdominal aortic aneurysm (AAA).Methods. ApoE−/−mice were randomly divided into 3 groups: AngII group, AngII + curcumin (AngII + Cur) group (100 mg/kg/d), and the control group. Miniosmotic pumps were implanted subcutaneously in ApoE−/−mice to deliver AngII for 28 days. After 4-week treatment, abdominal aortas with AAA were obtained for H&E staining, immunohistochemistry, and Western blotting.Results. The results showed that curcumin treatment significantly decreased the occurrence of AAA. The levels of macrophage infiltration, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factors-α(TNF-α) were significantly lower in AngII + Cur group than those in AngII group (allP<0.01). The level of superoxide dismutase (SOD) was significantly higher in AngII + Cur group than those in AngII groupP<0.01. The ERK1/2 phosphorylation in AngII + Cur group was significantly lower than that in AngII groupP<0.01.Conclusions. These results suggested that curcumin can inhibit the AngII-induced AAA in ApoE−/−mice, whose mechanisms include the curcumin anti-inflammation, antioxidative stress, and downregulation of ERK signaling pathway.


2017 ◽  
Vol 131 (22) ◽  
pp. 2707-2719 ◽  
Author(s):  
Carlos-Ernesto Fernandez-García ◽  
Carlos Tarin ◽  
Raquel Roldan-Montero ◽  
Diego Martinez-Lopez ◽  
Monica Torres-Fonseca ◽  
...  

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients (n=225) compared with the control group (n=100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA.


2020 ◽  
Vol 13 (2) ◽  
pp. 151-157
Author(s):  
Ryo Kanamoto ◽  
Hiroki Aoki ◽  
Aya Furusho ◽  
Hiroyuki Otsuka ◽  
Yusuke Shintani ◽  
...  

Author(s):  
O. Karaarslan Cengiz ◽  
G. Nergizoglu

The risk of cardiovascular disease begins to increase from the early stages of chronic kidney disease (CKD). Abdominal aortic aneurysms are the most common arterial aneurysms of peripheral arterial diseases. The frequency of abdominal aortic aneurysm varies according to the population studied. This study aimed to determine the prevalence of abdominal aortic aneurysm in patients with stage 3-4  CKD and investigate  CKD is a risk factor for abdominal aortic aneurysm formation. Methods. Patients aged 55 years and older who were followed up in the internal medicine outpatient clinics were enrolled. Two hundred CKD patients with glomerular filtration rates between 15-59 mL/min per 1.73 m2 were included in the study group, and 110 patients with glomerular filtration rates of 60 mL/min per 1.73 m2 or above were assigned to the control group. An ultrasonography device with a 3.5 MHz probe was used for screening. Abdominal aortic diameters of 3 cm and above were accepted as abdominal aortic aneurysms. Results. Eighteen patients in the study group (9%) and four in the control group (3.6%) had an abdominal aortic aneurysm. The prevalence of abdominal aortic aneurysms was higher in the  CKD  group. However, the difference was not statistically significant (p=0.078). Moreover, the median aortic diameter was 21.8 mm (14-44 mm) in the study group, compared to 21.0 mm (14-46 mm) in the control group. The prevalence of the abdominal aortic aneurysm was 14.9% in stage 4  CKD patients and 6% in stage 3  CKD patients (p=0.038). Conclusion. An abdominal aortic aneurysm is more common in patients with  CKD although it does not reach statistical significance. The median aortic diameter was significantly wider in CKD patients compared to the control group . The prevalence of abdominal aortic aneurysm increased with an increase in the CKD stage .


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