| 1. |
- Paloschi, V., 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. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 31:3, s. 691-7
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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 (rho=0.58) but not in BAV (rho=0.15) patients. Protein analyses of EDA-FN showed concordant results. Transforming growth factor-beta 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-beta 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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| 2. |
- Yousry, M., et al.
(författare)
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Real-time imaging required for optimal echocardiographic assessment of aortic valve calcification
- 2012
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 32:6, s. 470-475
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Aortic valve calcification (AVC), even without haemodynamic significance, may be prognostically import as an expression of generalized atherosclerosis, but techniques for echocardiographic assessment are essentially unexplored. Methods Two-dimensional (2D) echocardiographic recordings (Philips IE33) of the aortic valve in short-axis and long-axis views were performed in 185 consecutive patients within 1 week before surgery for aortic stenosis (n = 109, AS), aortic regurgitation (n = 61, AR), their combination (n = 8) or dilation of the ascending aorta (n = 7). The grey scale mean (GSMn) of the aortic valve in an end-diastolic short-axis still frame was measured. The same frame was scored visually 15 as indicating that the aortic valve was normal, thick, or had mild, moderate or severe calcification. The visual echodensity of each leaflet was determined real time applying the same 5-grade scoring system for each leaflet, and the average for the whole valve was calculated. Finally, a similar calcification score for the whole valve based on inspection and palpation by the surgeon was noted. Results Visual assessment of real-time images using the proposed scoring system showed better correlation with the surgical evaluation of the degree of valve calcification (r = 0.83, P<0.001) compared to evaluation of stop frames by visual assessment (r = 0.66, P<0.001) or the GSMn score (r = 0.64, P<0.001). High inter- and intra-observer correlations were observed for real-time visual score (both intraclass correlation coefficient = 0.93). Conclusion Real-time evaluation of the level of AVC is superior to using stop frames assessed either visually or by dedicated computer grey scale measurement software.
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| 3. |
- Aminoff, A, et al.
(författare)
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Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
- 2010
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Ingår i: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
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Tidskriftsartikel (refereegranskat)abstract
- Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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| 4. |
- Brack, Werner, et al.
(författare)
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The SOLUTIONS project : Challenges and responses for present and future emerging pollutants in land and water resources management
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 503, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- SOLUTIONS (2013 to 2018) is a European Union Seventh Framework Programme Project (EU-FP7). The project aims to deliver a conceptual framework to support the evidence-based development of environmental policies with regard to water quality. SOLUTIONS will develop the tools for the identification, prioritisation and assessment of those water contaminants that may pose a risk to ecosystems and human health. To this end, a new generation of chemical and effect-based monitoring tools is developed and integrated with a full set of exposure, effect and risk assessment models. SOLUTIONS attempts to address legacy, present and future contamination by integrating monitoring and modelling based approaches with scenarios on future developments in society, economy and technology and thus in contamination. The project follows a solutions-oriented approach by addressing major problems of water and chemicals management and by assessing abatement options. SOLUTIONS takes advantage of the access to the infrastructure necessary to investigate the large basins of the Danube and Rhine as well as relevant Mediterranean basins as case studies, and puts major efforts on stakeholder dialogue and support. Particularly, the EU Water Framework Directive (WFD) Common Implementation Strategy (CIS) working groups, International River Commissions, and water works associations are directly supported. with consistent guidance for the early detection, identification, prioritisation, and abatement of chemicals in the water cycle. SOLUTIONS will give a specific emphasis on concepts and tools for the impact and risk assessment of complex mixtures of emerging pollutants, their metabolites and transformation products. Analytical and effect-based screening tools will be applied together with ecological assessment tools for the identification of toxicants and their impacts. The SOLUTIONS approach is expected to provide transparent and evidence-based candidates or River Basin Specific Pollutants in the case study basins and to assist future review of priority pollutants under the WFD as well as potential abatement options.
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