| 1. |
- Folkersen, Lasse, et al.
(författare)
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Unraveling Divergent Gene Expression Profiles in Bicuspid and Tricuspid Aortic Valve Patients with Thoracic Aortic Dilatation: The ASAP Study
- 2011
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Ingår i: Molecular Medicine. - : Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 17:11-12, s. 1365-1373
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Tidskriftsartikel (refereegranskat)abstract
- Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (less than4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.
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| 2. |
- Paloschi, Valentina, et al.
(författare)
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Impaired Splicing of Fibronectin Is Associated With Thoracic Aortic Aneurysm Formation in Patients With Bicuspid Aortic Valve
- 2011
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 31:3, s. 691-697
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Thoracic aortic aneurysm is a common complication in patients with bicuspid aortic valve (BAV). Alternatively spliced extra domain A (EDA) of fibronectin (FN) has an essential role in tissue repair. Here we analyze the expression of FN spliceforms in dilated and nondilated ascending aorta of tricuspid aortic valve (TAV) and BAV patients.METHODS AND RESULTS:The mRNA expression was analyzed in the ascending aorta by Affymetrix Exon arrays in patients with TAV (n=40) and BAV (n=69). EDA and extra domain B (EDB) expression was increased in dilated aorta from TAV patients compared with nondilated aorta (P<0.001 and P<0.05, respectively). In contrast, EDA expression was not increased in dilated aorta from BAV patients (P=0.25), whereas EDB expression was upregulated (P<0.01). The expression of EDA correlated with maximum aortic diameter in TAV (ρ=0.58) but not in BAV (ρ=0.15) patients. Protein analyses of EDA-FN showed concordant results. Transforming growth factor-β treatment influenced the splicing of FN and enhanced the formation of EDA-containing FN in cultured medial cells from TAV patients but not in cells derived from BAV patients. Gene set enrichment analysis together with multivariate and univariate data analyses of mRNA expression suggested that differences in the transforming growth factor-β signaling pathway may explain the impaired EDA inclusion in BAV patients.CONCLUSIONS:Decreased EDA expression may contribute to increased aneurysm susceptibility of BAV patients.
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| 3. |
- Petrini, Johan, et al.
(författare)
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Circumferential strain by velocity vector imaging and speckle-tracking echocardiography : validation against sonomicrometry in an aortic phantom
- 2018
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Ingår i: Clinical Physiology and Functional Imaging. - : John Wiley & Sons. - 1475-0961 .- 1475-097X. ; 38:2, s. 269-277
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evaluation of arterial deformation and mechanics using strain analysis on ultrasound greyscale images has gained increasing scientific interest. The aim of this study was to validate in vitro measurements of circumferential strain by velocity vector imaging (VVI) and speckle-tracking echocardiography (STE) against sonomicrometry as a reference method. Method: Two polyvinyl alcohol phantoms sized to mimic the descending aorta were constructed and connected to a pulsatile flow pump to obtain high-resistance flow profiles. The ultrasound images of the phantom used for strain analyses were acquired with a transesophageal probe. Global and regional circumferential strains were estimated using VVI and STE and were compared with the strain acquired by sonomicrometry. Results: Global circumferential peak strain estimated by VVI and STE correlated well to sonomicrometry (r = 0·90, P≤0·001; and r = 0·97, P≤0·01) with a systematic bias of −0·78% and +0·63%, respectively. The reference strain levels were 1·07–2·54%. Circumferential strain values obtained by VVI were significantly lower than those obtained by STE (bias −1·41%, P≤0·001). Conclusion: Global circumferential strain measured by VVI and STE correlates well with sonomicrometry. However, strain values obtained by VVI and STE differ significantly, which should be taken into consideration when comparing results from studies using different software for aortic strain measurements.
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| 4. |
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| 5. |
- Petrini, Johan, 1975-
(författare)
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Querying RDF Schema Views of Relational Databases
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The amount of data found on the web today and its lack of semantics makes it increasingly harder to retrieve a particular piece of information. With the Resource Description Framework (RDF) every piece of information can be annotated with properties describing its semantics. The higher level language RDF Schema (RDFS) is defined in terms of RDF and provides means to describe classes of RDF resources and properties defined over these classes. Queries over RDFS data can be specified using the standard query language SPARQL. Since the majority of information in the world still resides in relational databases it should be investigated how to view and query their contents as views defined in terms of RDFS meta-data descriptions. However, processing of queries to general RDFS views over relational databases is challenging since the queries and view definitions are complex and the amount of data often is huge. A system, Semantic Web Abridged Relational Databases (SWARD), is developed to enable efficient processing of SPARQL queries to RDFS views of data in existing relational databases. The RDFS views, called universal property views (UPVs), are automatically generated provided a minimum of user input. A UPV is a general RDFS view of a relational database representing both its schema and data. Special attention is devoted to making the UPV represent as much of the relational database semantics as possible, including foreign and composite keys. A general query reduction algorithm, called PARtial evaluation of Queries (PARQ), for queries over complex views, such as UPVs, has been developed. The reduction algorithm is based on the program transformation technique partial evaluation. For UPVs, the PARQ algorithm is shown to elegantly reduce queries dramatically before regular cost-based optimization by a back-end relational DBMS. The results are verified by performance measurements of SPARQL queries to a commercial relational database.
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| 6. |
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| 7. |
- Petrini, Johan, et al.
(författare)
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Scalable RDF Views of Relational Databases through Partial Evaluation
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The semantic web represents meta-data as a triple relation using the RDF data model. We have developed a system to process queries to RDF views of entire relational databases. Optimization of queries to such views is challenging because i) RDF views of entire relational databases become large unions, and ii) queries to the views are more general than relational database queries, making no clear distinction between data and schema. As queries need not be expressed in terms of a schema, it becomes critical to optimize not only data access time but also the time to perform the query optimization itself. We have developed novel query optimization techniques for scalable queries to RDF views of relational databases. Our optimization techniques are based on partial evaluation, a method for compile time evaluation of subexpressions. We show dramatic improvements in query optimization time when scaling the query size while still producing high quality execution plans. Our query optimization techniques enable execution of real-world queries to RDF views of relational databases.
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| 8. |
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| 9. |
- Petrini, Johan
(författare)
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Vascular function in bicuspid aortic valve disease
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aortic valve normally consists of three cusps (tricuspid aortic valve, TAV), but in 0.5-2% of the population it consists of only two cusps (bicuspid aortic valve, BAV), which is the most common congenital cardiac malformation. BAV is prone to aortic stenosis (AS) and regurgitation (AR), and >25% of BAV patients will require surgery of the aortic valve and/or aorta within 20 years of diagnosis. BAV is associated with impaired function, dilation and dissection of the ascending aorta, while little is known about the abnormalities of the descending aorta in BAV. The aims of this thesis were to investigate morphological and functional alterations in the aorta of BAV and TAV patients, with a focus on the descending aorta, and to assess the feasibility of a new ultrasound-based method for studies of the elastic properties of the aorta. This was performed using transesophageal echocardiography (TEE) in consecutive patients without significant coronary artery disease having aortic valve disease and/or ascending aortic aneurysms requiring surgery (>50 % with BAV). In Study I (n = 300), we examined if different phenotypes of BAV (according to surgical inspection) were associated with different types of ascending aortic dilation. We did not find any such association. Ascending aortic dilation was common in patients with AS and BAV but not with TAV. In Study II (n = 85), a new modality, Velocity Vector Imaging (VVI), which is based on speckle tracking, was evaluated for automated deformation analysis of the descending aorta using TEE images. The method was found to be feasible for aortic studies. We could compute elasticity indices of the aorta with low variability and a strong correlation to indices calculated with a standard method (M-mode). In Study III (n = 192), we used VVI to compare aortic elasticity between BAV and TAV patients. After correction for age, dimension of the ascending aorta, cholesterol, and stroke volume in a multivariable regression model, BAV was associated with lower strain and distensibility of the descending aorta in the AR group, and higher distensibility in the AS group. In Study IV (n = 369), we examined the intima-media thickness (IMT) in the descending aorta and found no difference between BAV and TAV. Thus, the functional alterations of the aorta found in Study III seem not to depend on structural wall changes. Furthermore, we could show that genetic markers (single nucleotide polymorphisms, SNPs), which influence IMT in the carotid artery seem to correlate to IMT in the descending aorta in patients with TAV. In conclusion, we found no association between dilation of the ascending aorta and a specific BAV phenotype. We demonstrated that VVI technique is feasible for analysis of elastic properties of the aorta. In patients with AR, BAV was associated with lower strain and distensibility than TAV, suggesting impairment of the elastic aortic properties in the descending aorta. IMT was not influenced by presence of BAV.
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