scholarly journals Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tong Jiao ◽  
Ye Yao ◽  
Bo Zhang ◽  
Da-Cheng Hao ◽  
Qing-Feng Sun ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Mrna Expression ◽  
Posttranscriptional Regulation ◽  
Specific Inhibitor ◽  
Cellular Level ◽  
Vital Role ◽  
Abdominal Aortic ◽  
And Control

MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate 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

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.

Abstract 9781: Deletion of Prolyl Hydroxylase Domain Protein 2 in Myeloid Lineage suppressed Experimental Abdominal Aortic Aneurysm via NF-κB Inactivation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tomotake Tokunou ◽  
Chikahiro Sankoda ◽  
Aya Watanabe ◽  
Yusuke Takahara ◽  
Hiroshi Kojima ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Peritoneal Macrophages ◽  
Binding Activity ◽  
Abdominal Aortic ◽  
Domain Protein

Background: Macrophage migration to the vessels is important for vascular inflammation and induces vascular degenerative diseases. Macrophages secrete matrix metalloprotainases (MMPs), which activate many cytokines and digest extracellular matrix of aorta. MMPs play an important role in the progression of aortic aneurysm. We previously reported that non-specific prolyl hydroxylase domain protein (PHD) inhibitor, Cobalt chloride (CoCl2), suppressed MMP-2 and -9 expression and attenuated experimental abdominal aortic aneurysm (AAA) formation in mice. In this report we investigated the myeloid specific PHD2 knockout effect on MMPs expression and aneurysm formation. Methods: Myeloid specific PHD2 conditional knockout (MyPHD2KO) mice were generated. Experimental AAA was induced by periaortic application of Calcium chloride (CaCl2) for 6 weeks. In vitro Lipopolysaccharide (LPS, 100ng/ml) was used to induce MMP-2 and MMP-9 expression with peritoneal macrophages. MMPs mRNA, protein expression and protein activity were analyzed by qRT-PCR, Western blot analysis and Zymography, respectively. ELISA-based NF-κB p65 Transcription Factor Assay was used to examine NF-κB p65 binding activity with consensus DNA binding site. Results: CaCl2-induced AAA was suppressed with MyPHD2KO mice (max diameter of aneurysm: 1.03mm±0.14mm in MyPHD2KO group, 1.63mm±0.34mm in Control AAA group, p<0.01). In peritoneal macrophages CoCl2 reduced LPS-induced MMP-2 and MMP-9 mRNA and protein expression. PHD2 deletion in peritoneal macrophages from MyPHD2KO mice also suppressed LPS-induced MMP-2 and MMP-9 mRNA, protein expression and activity. PHD2 deletion suppressed LPS-induced NF-κB p65 phosphorylation via IκBα stabilization by Western blot analysis. NF-κB p65 binding activity was suppressed in MyPHD2KO macrophages (p<0.01 vs control). Conclusion: Deletion of PHD2 in myeloid lineage attenuated MMPs expression by NF-κB inactivation and suppressed AAA formation. PHD2 in macrophage may be a novel target for cardiovascular disease treatment.

Investigation of Plasma Inflammatory Profile in Diabetic Patients With Abdominal Aortic Aneurysm: A Pilot Study

2018 ◽  
Vol 52 (8) ◽  
pp. 597-601 ◽  
Author(s):  
Fabien Lareyre ◽  
Claudine Moratal ◽  
Julien Chikande ◽  
Elixène Jean-Baptiste ◽  
Réda Hassen-Khodja ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Negative Association ◽  
Diabetic Patients ◽  
Protein Biomarkers ◽  
Abdominal Aortic ◽  
Tumor Necrosis Factor Ligand ◽  
Lower Protein ◽  
Inflammatory Profile

Introduction: Clinical studies have unraveled a negative association between diabetes and abdominal aortic aneurysm (AAA), but the mechanisms involved are still poorly understood. The aim of this study was to determine whether diabetic patients with AAA had a distinct plasma inflammatory profile compared to nondiabetic patients. Methods: Plasma samples were obtained from 10 diabetic patients with AAA and 10 nondiabetic patients with AAA. The relative protein expression of 92 inflammatory-related human protein biomarkers was assessed by proximity extension assay technology using Proseek Multiplex Inflammation I kit (Olink). Results: Clinical characteristics were similar in diabetic patients with AAA compared to nondiabetic patients with AAA, the median ages being 67 and 73 years, respectively ( P = .61). The AAA diameters were, respectively, 50 and 49 mm ( P = .72). Among the 92 markers screened, 67 (72.8%) were detected in all samples. Diabetic patients had significantly lower protein expression of C-C motif chemokine 19 (CCL19) and C-C motif chemokine 23 (CCL23; 542.3 vs 980.3, P = .01 and 1236 vs 1406, P = .04, respectively). They tended to have higher expression of tumor necrosis factor ligand superfamily member 14 (TNFSF14) compared to controls (14.6 vs 10.8, P = .05). Conclusion: Diabetic patients with AAA differentially expressed CCL19, CCL23 and TNFSF14 in plasma compared to nondiabetic patients with AAA. Further studies are required to determine whether the markers identified could play a role in the negative association between diabetes and AAA pathogenesis.

scholarly journals Galectin-3 as a Biomarker for Stratifying Abdominal Aortic Aneurysm Size in a Taiwanese Population

2021 ◽  
Vol 8 ◽  
Author(s):  
Hsin-Ying Lu ◽  
Chun-Ming Shih ◽  
Shih-Hsien Sung ◽  
Alexander T. H. Wu ◽  
Tsai-Mu Cheng ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Characteristic Curve ◽  
Multivariate Logistic Regression Analysis ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Abdominal Aortic ◽  
Galectin 3 ◽  
Inflammatory Processes ◽  
And Control

Abdominal aortic aneurysm (AAA) ruptures are unpredictable and lethal. A biomarker predicting AAA rupture risk could help identify patients with small, screen-detected AAAs. Galectin-3 (Gal-3), a β-galactosidase–binding lectin, is involved in inflammatory processes and may be associated with AAA incidence. We investigated whether Gal-3 can be used as a biomarker of AAA size. Plasma Gal-3 protein concentrations were examined in patients with AAA (n = 151) and control patients (n = 195) using Human ProcartaPlex multiplex and simplex kits. Circulating Gal-3 levels were significantly higher in patients with AAA than in control patients. The area under the receiver operating characteristic curve for Gal-3 was 0.91. Multivariate logistic regression analysis revealed a significant association between Gal-3 level and the presence of AAA. Circulating Gal-3 levels were significantly correlated with aortic diameter in a concentration-dependent manner. In conclusion, higher plasma Gal-3 concentrations may be a useful biomarker of AAA progression.

scholarly journals Targeting Tyrosine Hydroxylase for Abdominal Aortic Aneurysm: Impact on Inflammation, Oxidative Stress, and Vascular Remodeling

Hypertension ◽  
2021 ◽  
Author(s):  
Laia Cañes ◽  
Judith Alonso ◽  
Carme Ballester-Servera ◽  
Saray Varona ◽  
José R. Escudero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Abdominal Aortic Aneurysm ◽  
Tyrosine Hydroxylase ◽  
Aortic Aneurysm ◽  
Specific Inhibitor ◽  
Orphan Receptor ◽  
Matrix Metalloproteinase 2 ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
The Impact

Pharmacological treatments for preventing abdominal aortic aneurysm (AAA) rupture or slowing aneurysm progression remain a challenge. It is increasingly recognized that sympathetic activity might play a role in the pathogenesis of AAA; however, the impact of this pathway remains unclear. Here, we show that the expression of tyrosine hydroxylase ( TH ), dopamine β-hydroxylase ( DBH ), and the norepinephrine transporter SLC6A2 is upregulated in abdominal aorta samples from AAA patients and in the aneurysmal aorta from 2 animal models susceptible to Ang II (angiotensin II)–induced AAA: the apolipoprotein E-deficient (ApoE −/− ) model and a transgenic mouse that overexpresses the human nuclear receptor NOR-1 (neuron-derived orphan receptor-1) in the vascular wall (TgNOR-1 VSMC ). TH localizes to sympathetic nerves innervating the local vasculature, but also to inflammatory cells, and scattered vascular smooth muscle cell in human and mouse AAA. Interestingly, the preventive effect of doxycycline on AAA formation in Ang II–treated TgNOR-1 VSMC mice was associated to the normalization of vascular Th expression. Moreover, the TH specific inhibitor α-methyl- p -tyrosine protected against Ang II–induced AAA formation, limiting the progressive increase in aortic diameter without affecting blood pressure. The drug normalized MMP2 (matrix metalloproteinase 2) expression and MMP activity, preserving elastin integrity, attenuated the Ang II–mediated rise in vascular oxidative stress and inflammatory markers and reduced the inflammatory infiltrate. Finally, NOR-1, whose expression correlated with that of TH in human AAA, was able to drive human TH transcriptional activity in transient transfection assays. Therefore, the upregulation of the TH pathway could be critical in the pathophysiology of AAA, supporting the potential of pharmacological strategies targeting TH for AAA management.

A Pilot Study of Protein Microarray for Simultaneous Analysis of 274 Cytokines Between Abdominal Aortic Aneurysm and Normal Aorta

Angiology ◽  
2019 ◽  
Vol 70 (9) ◽  
pp. 830-837 ◽  
Author(s):  
Li Yuwen ◽  
Yang Ciqiu ◽  
Shi Yi ◽  
Liu Ruilei ◽  
Lai Yuanhui ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Expression Profile ◽  
Protein Microarray ◽  
Cytokine Expression ◽  
Protein Array ◽  
Differentially Expressed ◽  
Cytokine Expression Profile ◽  
Abdominal Aortic ◽  
And Control

Cytokines play an important role in the pathogenesis of abdominal aortic aneurysm (AAA). We evaluated the cytokine expression profile of large AAA walls using a 274-cytokine protein array. We hypothesized that AAAs are characterized by an inflammatory, chemotactic cytokine profile. We investigated the cytokine expression profile of 12 patients with AAA and 6 nonaneurysmal controls using an antibody-based protein array. The array generated antibodies against homogenized human aortic tissues to validate the cytokines differentially expressed in AAAs and normal aortas. Data were quantified using fluorescent signal intensities and statistically analyzed by the t test. Fifty-nine cytokines were differentially expressed between the AAA and control samples. Of the 35 selected cytokines that had relative expression >1000, 29 were significantly higher and 6 were lower in AAA samples than in controls. They respectively belonged to CC chemokines, CXC chemokines, pro-inflammatory cytokines, growth factors, proteolytic proteins and inhibitors, and cell adhesion cytokines. Our results show that distinct cytokines are involved in AAAs and suggest that the pathways involving these cytokines may be associated with the pathogenesis and development of AAAs. These findings, if confirmed by larger studies, may suggest treatment targets.

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 Gene and Protein Expression is Associated with Hypoxia in the Human Abdominal Aortic Aneurysm (AAA) Wall

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
David Alan Vorp ◽  
Anton E. Xavier ◽  
Douglas W. Chew ◽  
Deborah A. Cleary ◽  
Melissa A. Morgan ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Expression ◽  
Abdominal Aortic ◽  
Gene And Protein Expression ◽  
Differential Gene

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
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Inflammatory Response ◽  
Cell Apoptosis ◽  
Cellular Level ◽  
Control Group ◽  
Expression Plasmid ◽  
Over Expression ◽  
Abdominal Aortic ◽  
Ecm Degradation

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.

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