scholarly journals ELUCIDATING THE MOLECULAR MECHANISMS OF MIR-26A ON THE PATHOGENESIS OF ABDOMINAL AORTIC ANEURYSM - IN VITRO STUDIES

2018 ◽  
Vol 34 (10) ◽  
pp. S69-S70
Author(s):  
L. Elfaki ◽  
R. Pirani ◽  
Z. Afrasiabi ◽  
P. Matkar ◽  
H. Chen ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Molecular Mechanisms ◽  
In Vitro Studies ◽  
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 IKK Epsilon Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Inhibiting Inflammation, Oxidative Stress, and Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Hao Chai ◽  
ZhongHao Tao ◽  
YongChao Qi ◽  
HaoYu Qi ◽  
Wen Chen ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Ang Ii ◽  
Elastin Degradation ◽  
Maximal Diameter ◽  
Abdominal Aortic ◽  
Primary Mouse

Abdominal aortic aneurysm (AAA) is a vascular disorder that is considered a chronic inflammatory disease. However, the precise molecular mechanisms involved in AAA have not been fully elucidated. Recently, significant progress has been made in understanding the function and mechanism of action of inhibitor of kappa B kinase epsilon (IKKε) in inflammatory and metabolic diseases. The angiotensin II- (Ang II-) induced or pharmacological inhibitors were established to test the effects of IKKε on AAA in vivo. After mice were continuously stimulated with Ang II for 28 days, morphologically, we found that knockout of IKKε reduced AAA formation and drastically reduced maximal diameter and severity. We also observed a decrease in elastin degradation and medial destruction, which were independent of systolic blood pressure or plasma cholesterol concentrations. Western blot analyses and immunohistochemical staining were carried out to measure IKKε expression in AAA tissues and cell lines. AAA phenotype of mice was measured by ultrasound and biochemical indexes. In zymography, immunohistology staining, immunofluorescence staining, and reactive oxygen species (ROS) analysis, TUNEL assay was used to examine the effects of IKKε on AAA progression in AAA mice. IKKε deficiency significantly inhibited inflammatory macrophage infiltration, matrix metalloproteinase (MMP) activity, ROS production, and vascular smooth muscle cell (VSMC) apoptosis. We used primary mouse aortic VSMC isolated from apolipoprotein E (Apoe) −/− and Apoe−/−IKKε−/− mice. Mechanistically, IKKε deficiency blunted the activation of the ERK1/2 pathway. The IKKε inhibitor, amlexanox, has the same impact in AAA. Our results demonstrate a critical role of IKKε in AAA formation induced by Ang II in Apoe−/− mice. Targeting IKKε may constitute a novel therapeutic strategy to prevent AAA progression.

scholarly journals Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

2020 ◽  
Vol 21 (17) ◽  
pp. 6334
Author(s):  
Rijan Gurung ◽  
Andrew Mark Choong ◽  
Chin Cheng Woo ◽  
Roger Foo ◽  
Vitaly Sorokin
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Aortic Wall ◽  
Epigenetic Mechanisms ◽  
Phenotypic Modulation ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.

Development of fibrinous thrombus analogue for in-vitro abdominal aortic aneurysm studies

2007 ◽  
Vol 40 (2) ◽  
pp. 289-295 ◽  
Author(s):  
J.W. Hinnen ◽  
D.J. Rixen ◽  
O.H.J. Koning ◽  
J.H. van Bockel ◽  
J.F. Hamming
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Abdominal Aortic

scholarly journals Bioinformatics analysis of potential common molecular pathogenesis assumed by intracranial aneurysm, aortic aneurysm and aortic dissection

2021 ◽  
Author(s):  
Chao Zhao ◽  
Xinchun Cui ◽  
Guodong Liu ◽  
Jianlong Li ◽  
Jinxing Liu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Dissection ◽  
Intracranial Aneurysm ◽  
Molecular Mechanisms ◽  
Biological Processes ◽  
Network Analyses ◽  
Abdominal Aortic ◽  
Genetic Overlap ◽  
Pathogenesis Related

Abstract This study is intended to find possible pathogenesis-related genetic overlap and common molecular mechanisms of intracranial aneurysm, abdominal aortic aneurysm and aortic dissection. Three mRNA microarray datasets,GSE75436 of intracranial aneurysms, GSE7084 of abdominal aortic aneurysm and GSE52093 of aortic dissection were downloaded from Gene Expression Omnibus and detected in silico . DEGs of these three datasets screened through GEO2R, respectively . The overlapping genes were found by Venny mapping. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and Genomespathway enrichment analysiswere performed using the DAVID database and protein-protein interaction network analyses were conducted by STRING and Cytoscape webpage tool to illustrate the molecular mechanisms in their pathogenesis and progression.This study identified 178 DEGs, including SMTN, MYH11, TAGLN, ACTG2, CNN1, MYLK, LMOD1, MYL9,VCL and ACTC1 in the the most significant module. Except for those confirmed biological processes, mesenchyme migration and platelet aggregation are common biological processes shared by genes in the most significant module and the hub genes. Focal adhesionssignaling pathway is highlighted in this analysis. The present study identified possible pathogenesis-related genetic overlap and common molecular mechanisms of intracranial aneurysm, abdominal aortic aneurysm and aortic dissection, which may contribute to their diagnosis, treatment and prognostic prediction with a systematic view.

The Development of Physiological Compliant Abdominal Aortic Aneurysm Models for In Vitro Flow Studies

2009 ◽  
Author(s):  
Timothy J. Corbett ◽  
Barry J. Doyle ◽  
Anthony Callanan ◽  
Tim M. McGloughlin
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Material Properties ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Flow Loop ◽  
The Past ◽  
Abdominal Aortic

A vast amount of experimental research has been undertaken in the past decade to investigate different aspects of preoperative and postoperative abdominal aortic aneurysms (AAAs). Much of this research has been based on the use of mock arteries in an in vitro flow loop to mimic the behaviour of the abdominal aorta in vivo [1]. These models should be reproducible, have consistent material properties, consistent thickness and be physiological in behaviour.

scholarly journals Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

2008 ◽  
Vol 32 (6) ◽  
pp. 976-986 ◽  
Author(s):  
Suman Annambhotla ◽  
Sebastian Bourgeois ◽  
Xinwen Wang ◽  
Peter H. Lin ◽  
Qizhi Yao ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Molecular Mechanisms ◽  
Aneurysm Formation ◽  
Recent Advances ◽  
Abdominal Aortic

scholarly journals Cyclic nucleotide phosphodiesterase 1C contributes to abdominal aortic aneurysm

2021 ◽  
Vol 118 (31) ◽  
pp. e2107898118
Author(s):  
Chongyang Zhang ◽  
Hongmei Zhao ◽  
Yujun Cai ◽  
Jian Xiong ◽  
Amy Mohan ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cyclic Nucleotide ◽  
Aortic Aneurysms ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Causative Role ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is characterized by aorta dilation due to wall degeneration, which mostly occurs in elderly males. Vascular aging is implicated in degenerative vascular pathologies, including AAA. Cyclic nucleotide phosphodiesterases, by hydrolyzing cyclic nucleotides, play critical roles in regulating vascular structure remodeling and function. Cyclic nucleotide phosphodiesterase 1C (PDE1C) expression is induced in dedifferentiated and aging vascular smooth muscle cells (SMCs), while little is known about the role of PDE1C in aneurysm. We observed that PDE1C was not expressed in normal aorta but highly induced in SMC-like cells in human and murine AAA. In mouse AAA models induced by Angiotensin II or periaortic elastase, PDE1C deficiency significantly decreased AAA incidence, aortic dilation, and elastin degradation, which supported a causative role of PDE1C in AAA development in vivo. Pharmacological inhibition of PDE1C also significantly suppressed preestablished AAA. We showed that PDE1C depletion antagonized SMC senescence in vitro and/or in vivo, as assessed by multiple senescence biomarkers, including senescence-associated β-galactosidase activity, γ-H2AX foci number, and p21 protein level. Interestingly, the role of PDE1C in SMC senescence in vitro and in vivo was dependent on Sirtuin 1 (SIRT1). Mechanistic studies further showed that cAMP derived from PDE1C inhibition stimulated SIRT1 activation, likely through a direct interaction between cAMP and SIRT1, which leads to subsequent up-regulation of SIRT1 expression. Our findings provide evidence that PDE1C elevation links SMC senescence to AAA development in both experimental animal models and human AAA, suggesting therapeutical significance of PDE1C as a potential target against aortic aneurysms.

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