Dataset Information

The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.

ABSTRACT: The most important feature of abdominal aortic aneurysm (AAA) pathogenesis is an enzymatic degradation of elastic lamellae and extracellular matrix proteins particularly with participation of matrix metalloproteinases. Plasmin, which is responsible for the dissolution of fibrin in blood vessels, plays also a key role in the cascade for activation of the metalloproteinases. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for tissue plasminogen activator (-7351 C/T polymorphism), urokinase-type plasminogen activator (1788 C/T polymorphism) and plasminogen activator inhibitor 1 (-675 4G/5G and -844 G/A polymorphism) on the susceptibility to AAA. We performed a case-control study of 153 polish patients hospitalized due to AAA and compared them with matched healthy control subjects. The polymorphisms were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments or through high-resolution melting analysis. In this study we have found lower frequency of wild-type GG genotype of the -844G/A PAI-1 polymorphism in cases than in controls, what may suggest the protective effect of this genotype for the risk of AAA development. None of the remaining polymorphisms tested were associated with AAA occurrence.

SUBMITTER: Oszajca K

PROVIDER: S-EPMC4013441 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.

Oszajca Katarzyna K Wroński Konrad K Janiszewska Grażyna G Bieńkiewicz Małgorzata M Bartkowiak Jacek J Szemraj Janusz J

Molecular biology reports 20140123 5

The most important feature of abdominal aortic aneurysm (AAA) pathogenesis is an enzymatic degradation of elastic lamellae and extracellular matrix proteins particularly with participation of matrix metalloproteinases. Plasmin, which is responsible for the dissolution of fibrin in blood vessels, plays also a key role in the cascade for activation of the metalloproteinases. The purpose of this study was to evaluate the influence of selected polymorphisms in genes coding for tissue plasminogen act ...[more]

PMID: 24452721

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Project description:BackgroundAbdominal aortic aneurysm (AAA) is the full thickness dilation of the abdominal aorta. However, few effective medical therapies are available. Thus, elucidating the molecular mechanism of AAA pathogenesis and exploring the potential molecular target of medical therapies for AAA is of vital importance.MethodsThree expression datasets (GSE7084, GSE47472 and GSE57691) were downloaded from the Gene Expression Omnibus (GEO). These datasets were merged and then normalized using the "sva" R package. Differential expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were conducted. We compared the co-expression patterns between AAA and normal conditions, and hub genes of each functional module were identified. DEGs were mapped to co-expression network under AAA condition and a DEG co-expression network was generated. Crucial genes were identified using molecular complex detection (MCODE) (a plugin in Cytoscape).ResultsIn our study, 6 and 10 gene modules were detected for the AAA and normal conditions, respectively, while 143 DEGs were screened. Compared to the normal condition, genes associated with immune response, inflammation and muscle contraction were clustered in three gene modules respectively under the AAA condition; the hub genes of the three modules were MAP4K1, NFIB and HPK1, respectively. A DEG co-expression network with 102 nodes and 303 edges was identified, and a hub gene cluster with 10 genes from the DEG co-expression network was detected. YIPF6, RABGAP1, ANKRD6, GPD1L, PGRMC2, HIGD1A, GMDS, MGP, SLC25A4 and FAM129A were in the cluster. The expression levels of these 10 genes showed potential diagnostic value.ConclusionBased on WGCNA, we detected 6 modules under the AAA condition and 10 modules in the normal condition. Hub genes of each module and hub gene clusters of the DEG co-expression network were identified. These genes may act as potential targets for medical therapy and diagnostic biomarkers. Further studies are needed to elucidate the detailed biological function of these genes in the pathogenesis of AAA.

Project description:BackgroundRupture of abdominal aortic aneurysm (rAAA) is a fatal event in the elderly. Elevated blood pressure and weakening of vessel wall strength are major risk factors for this devastating event. This present study examined whether the expression profile of mechanosensitive genes correlates with the phenotype and outcome, thus, serving as a biomarker for AAA development.MethodsIn this study, we identified mechanosensitive genes involved in AAA development using general bioinformatics methods and machine learning with six human datasets publicly available from the GEO database. Differentially expressed mechanosensitive genes (DEMGs) in AAAs were identified by differential expression analysis. Molecular biological functions of genes were explored using functional clustering, Protein-protein interaction (PPI), and weighted gene co-expression network analysis (WGCNA). According to the datasets (GSE98278, GSE205071 and GSE165470), the changes of diameter and aortic wall strength of AAA induced by DEMGs were verified by consensus clustering analysis, machine learning models, and statistical analysis. In addition, a model for identifying AAA subtypes was built using machine learning methods.Results38 DEMGs clustered in pathways regulating 'Smooth muscle cell biology' and 'Cell or Tissue connectivity'. By analyzing the GSE205071 and GSE165470 datasets, DEMGs were found to respond to differences in aneurysm diameter and vessel wall strength. Thus, in the merged datasets, we formally created subgroups of AAAs and found differences in immune characteristics between the subgroups. Finally, a model that accurately predicts the AAA subtype that is more likely to rupture was successfully developed.ConclusionWe identified 38 DEMGs that may be involved in AAA. This gene cluster is involved in regulating the maximum vessel diameter, degree of immunoinflammatory infiltration, and strength of the local vessel wall in AAA. The prognostic model we developed can accurately identify the AAA subtypes that tend to rupture.

Project description:Approximately 13,000 people die of an abdominal aortic aneurysm (AAA) every year. This study aimed to identify the immune response-related genes that play important roles in AAA using bioinformatics approaches. We downloaded the GSE57691 and GSE98278 datasets related to AAA from the Gene Expression Omnibus database, which included 80 AAA and 10 normal vascular samples. CIBERSORT was used to analyze the samples and detect the infiltration of 22 types of immune cells and their differences and correlations. The principal component analysis showed significant differences in the infiltration of immune cells between normal vascular and AAA samples. High proportions of CD4+ T cells, activated mast cells, resting natural killer cells, and 12 other types of immune cells were found in normal vascular tissues, whereas high proportions of macrophages, CD8+ T cells, resting mast cells, and six other types of immune cells were found in AAA tissues. In the selected samples, we identified 39 upregulated (involved in growth factor activity, hormone receptor binding, and cytokine receptor activity) and 133 downregulated genes (involved in T cell activation, cell chemotaxis, and regulation of immune response mediators). The key differentially expressed immune response-related genes were screened using the STRING database and Cytoscape software. Two downregulated genes, PI3 and MAP2K1, and three upregulated genes, SSTR1, GPER1, and CCR10, were identified by constructing a protein-protein interaction network. Functional enrichment of the differentially expressed genes was analyzed, and the expression of the five key genes in AAA samples was verified using quantitative polymerase chain reaction, which revealed that MAP2K1 was downregulated in AAA, whereas SSTR1, GEPR1, and CCR10 were upregulated; there was no significant difference in PI3 expression. Our study shows that normal vascular and AAA samples can be distinguished via the infiltration of immune cells. Five genes, PI3, MAP2K1, SSTR1, GPER1, and CCR10, may play important roles in the development, diagnosis, and treatment of AAA.

Dataset Information

The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.

Publications

The study of t-PA, u-PA and PAI-1 genes polymorphisms in patients with abdominal aortic aneurysm.

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