Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development

2017 ◽  
Vol 131 (22) ◽  
pp. 2707-2719 ◽  
Author(s):  
Carlos-Ernesto Fernandez-García ◽  
Carlos Tarin ◽  
Raquel Roldan-Montero ◽  
Diego Martinez-Lopez ◽  
Monica Torres-Fonseca ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Potential Role ◽  
Control Group ◽  
Mrna Levels ◽  
Abdominal Aortic ◽  
Stat3 Phosphorylation ◽  
Galectin 3 ◽  
Mrna And Protein Expression

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.

scholarly journals Targeting MicroRNA-192-5p, a Downstream Effector of NOXs (NADPH Oxidases), Reverses Endothelial DHFR (Dihydrofolate Reductase) Deficiency to Attenuate Abdominal Aortic Aneurysm Formation

Hypertension ◽  
2021 ◽  
Author(s):  
Kai Huang ◽  
Taro Narumi ◽  
Yixuan Zhang ◽  
Qiang Li ◽  
Priya Murugesan ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Dihydrofolate Reductase ◽  
Homo Sapiens ◽  
Ang Ii ◽  
Downstream Effector ◽  
Abdominal Aortic ◽  
Mrna And Protein Expression

We have shown that endothelial-specific DHFR (dihydrofolate reductase) deficiency underlies eNOS (endothelial NO synthase) uncoupling and formation of abdominal aortic aneurysm (AAA). Here, we examined a novel role of microRNA-192-5p in mediating NOX (NADPH oxidase)-dependent DHFR deficiency and AAA formation. microRNA-192-5p is predicted to target DHFR. Intriguingly, homo sapiens–microRNA-192-5p expression was substantially upregulated in human patients with AAA. In human aortic endothelial cells exposed to hydrogen peroxide (H 2 O 2 ), homo sapiens–microRNA-192-5p expression was significantly upregulated. This was accompanied by a marked downregulation in DHFR mRNA and protein expression, which was restored by homo sapiens–microRNA-192-5p–specific inhibitor. Of note, microRNA-192-5p expression was markedly upregulated in Ang II (angiotensin II)–infused hph-1 (hyperphenylalaninemia 1) mice, which was attenuated in hph-1–NOX1, hph-1–NOX2, hph-1–neutrophil cytosol factor 1, and hph-1–NOX4 double mutant mice where AAA incidence was also abrogated, indicating a downstream effector role of microRNA-192-5p following NOX activation. In vivo treatment with mus musculus–microRNA-192-5p inhibitor attenuated expansion of abdominal aortas in Ang II–infused hph-1 mice as defined by ultrasound and postmortem inspection. It also reversed features of vascular remodeling including matrix degradation, adventitial hypertrophy, and formation of intraluminal thrombi. These animals had restored DHFR mRNA and protein expression, attenuated superoxide production, recoupled eNOS, and preserved NO bioavailability. In conclusion, our data for the first time demonstrate a critical role of microRNA-192-5p in mediating NOX-dependent DHFR deficiency and AAA formation, inhibition of which is robustly effective in attenuating development of AAA. Since the mouse and human microRNA-192-5p sequences are identical, the microRNA-192-5p inhibitors may be readily translatable into novel therapeutics for the treatment of AAA.

scholarly journals Differential Protein Expression in Serum of Abdominal Aortic Aneurysm Patients – A Proteomic Approach

2011 ◽  
Vol 42 (5) ◽  
pp. 563-570 ◽  
Author(s):  
B. Pulinx ◽  
F.A.M.V.I. Hellenthal ◽  
K. Hamulyák ◽  
M.P. van Dieijen-Visser ◽  
G.W.H. Schurink ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Differential Protein Expression ◽  
Differential Protein ◽  
Proteomic Approach ◽  
Abdominal Aortic

scholarly journals Identification of Novel Long Noncoding RNAs and Their Role in Abdominal Aortic Aneurysm

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Abulaihaiti Maitiseyiti ◽  
Hongbo Ci ◽  
Qingbo Fang ◽  
Sheng Guan ◽  
Alimujiang Shawuti ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Functional Enrichment ◽  
Pcr Analysis ◽  
Control Group ◽  
Abdominal Aortic

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.

scholarly journals Routine open abdomen treatment compared with on-demand open abdomen or direct closure following open repair of ruptured abdominal aortic aneurysms: A propensity score–matched study

2019 ◽  
Vol 7 ◽  
pp. 205031211983350 ◽  
Author(s):  
Kristian Smidfelt ◽  
Joakim Nordanstig ◽  
Urban Wingren ◽  
Göran Bergström ◽  
Marcus Langenskiöld
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Propensity Score ◽  
Open Abdomen ◽  
Open Repair ◽  
Matched Control ◽  
University Hospital ◽  
Control Group ◽  
Ruptured Abdominal Aortic Aneurysm ◽  
Abdominal Aortic

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.

scholarly journals Curcumin Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm by Inhibition of Inflammatory Response and ERK Signaling Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
QingQing Hao ◽  
Xu Chen ◽  
XiaoYu Wang ◽  
Bo Dong ◽  
ChuanHua Yang
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Erk Signaling ◽  
Control Group ◽  
Tumor Necrosis Factors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Age Related ◽  
Abdominal Aortic ◽  
Antioxidative Stress ◽  
Anti Inflammation

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.

scholarly journals A potential role for glycated cross-links in abdominal aortic aneurysm disease

2017 ◽  
Vol 65 (5) ◽  
pp. 1493-1503.e3 ◽  
Author(s):  
Dave Koole ◽  
Joost A. van Herwaarden ◽  
Casper G. Schalkwijk ◽  
Floris P.J.G. Lafeber ◽  
Aryan Vink ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Potential Role ◽  
Abdominal Aortic ◽  
Cross Links

scholarly journals Prevalenceof abdominal aortic aneurysm among stage 3-4 chronic kidney disease patients aged 55 years and older

2020 ◽  
pp. 9-16
Author(s):  
O. Karaarslan Cengiz ◽  
G. Nergizoglu
Keyword(s):  
Chronic Kidney Disease ◽  
Abdominal Aortic Aneurysm ◽  
Kidney Disease ◽  
Aortic Aneurysm ◽  
Glomerular Filtration ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Study Group ◽  
Abdominal Aortic

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 .

scholarly journals Calprotectin and Receptor for Advanced Glycation End Products as a Potential Biomarker in Abdominal Aortic Aneurysm

2020 ◽  
Vol 9 (4) ◽  
pp. 927
Author(s):  
Willy Hauzer ◽  
Wojciech Witkiewicz ◽  
Jan Gnus
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Advanced Glycation End Products ◽  
Endovascular Aneurysm Repair ◽  
Control Group ◽  
Advanced Glycation ◽  
Abdominal Aortic ◽  
Potential Biomarker ◽  
Glycation End Products ◽  
End Products

Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the diameter of the abdominal aorta was found. The purpose of this study was to investigate whether calprotectin and the RAGE plasma level may be a biomarker of human AAA occurrence. We determined two groups of research participants: a group of 32 patients aged 53–88 undergoing primary endovascular aneurysm repair and a control group of 43 volunteers aged 59–82 without the AAA. All the patients from the study group had their blood samples drawn in order to determine the level of calprotectin and RAGE in plasma. The second follow-up examination was carried out after three months. The concentration of calprotectin and RAGE in plasma was determined with the use of the immunoenzymatic method (ELISA). The study showed that patients with the AAA had significantly higher mean calprotectin and RAGE plasma levels (p = 0.0001 and p = 0.0002, respectively) as compared to the control group. After the AAA repair operations, the level of concentration of the calprotectin decreased significantly (p = 0.0002). So far, no studies on the connection between the increase of the calprotectin and RAGE in the patient’s plasma with the AAA have been published. Calprotectin may be a promising biomarker related to the occurrence of AAA. Larger studies are needed to fully elucidate and confirm the role of calprotectin in the development and progression of the aneurysm.

Diet and the content of selenium and lead in patients with abdominal aortic aneurysm

VASA ◽  
2011 ◽  
Vol 40 (5) ◽  
pp. 381-389 ◽  
Author(s):  
Socha ◽  
Borawska ◽  
Gacko ◽  
Guzowski
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Healthy Volunteers ◽  
Arterial Wall ◽  
Aortic Wall ◽  
Dietary Habits ◽  
Absorption Spectrometry ◽  
Control Group ◽  
Abdominal Aortic ◽  
The Mean

Background: To evaluate the content of selenium (Se) and lead (Pb) and the influence of dietary habits and smoking in patients with abdominal aortic aneurysm (AAA). Patients and methods: Forty-nine patients with AAA prior to surgical procedures aged 42 - 81 years and a control group of 22 healthy volunteers aged 31 - 72 years and 17 aortic wall samples from deceased were included in the study. Food-frequency questionnaires were implemented in AAA patients to collect the dietary data. Se and Pb concentrations in the serum and blood, respectively, and in arterial wall and parietal thrombus samples were determined by the atomic absorption spectrometry method. Results: The mean Se level in serum of patients with AAA (60.37 ± 21.2 microg/L) was significantly (p < 0.008) lower than in healthy volunteers (75.87 ± 22.4 microg/L). We observed a significant correlation (r = 0.69, p < 0.0001) between the content of Se in serum and the parietal thrombus of examined patients. Se concentration in aortic wall was inversely correlated to the concentration of Pb (r = - 0.38, p < 0.02). We observed significantly lower (p < 0.05) concentrations of Se (39.14 ± 37.1 microg/g) and significantly higher (p < 0.05) concentrations of Pb (202.69 ± 180.6 microg/g) in aortic wall samples of smoking patients than in non-smoking patients (77.56 ± 70.0 microg/g, 73.09 ± 49.8 microg/g; respectively). Conclusions: Se serum level is lower in patients with AAA than in healthy volunteers. In aortic wall, Se concentration is inversely correlated with Pb concentration. Dietary habits and smoking have an influence on the Se and Pb status in patients with AAA.

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