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- Skogsberg, J., et al.
(författare)
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Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes
- 2008
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr-/-Apo 100/100 Mttpflox/flox Mx1-Cre). Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins) at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies. © 2008 Skogsberg et al.
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- Gustafsson, Mika, et al.
(författare)
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Reverse Engineering of Gene Networks with LASSO and Nonlinear Basis Functions
- 2009
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Ingår i: CHALLENGES OF SYSTEMS BIOLOGY: COMMUNITY EFFORTS TO HARNESS BIOLOGICAL COMPLEXITY. - : Wiley. - 0077-8923 .- 1749-6632. ; 1158, s. 265-275
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Tidskriftsartikel (refereegranskat)abstract
- The quest to determine cause from effect is often referred to as reverse engineering in the context of cellular networks. Here we propose and evaluate an algorithm for reverse engineering a gene regulatory network from time-series kind steady-state data. Our algorithmic pipeline, which is rather standard in its parts but not in its integrative composition, combines ordinary differential equations, parameter estimations by least angle regression, and cross-validation procedures for determining the in-degrees and selection of nonlinear transfer functions. The result of the algorithm is a complete directed net-work, in which each edge has been assigned a score front it bootstrap procedure. To evaluate the performance, we submitted the outcome of the algorithm to the reverse engineering assessment competition DREAM2, where we used the data corresponding to the InSillico1 and InSilico2 networks as input. Our algorithm outperformed all other algorithms when inferring one of the directed gene-to-gene networks.
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- Johansson, C.S., et al.
(författare)
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Periodontal conditions in patients with coronary heart disease : A case-control study
- 2008
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Ingår i: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 35:3, s. 199-205
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study examined periodontal conditions in patients with coronary heart disease (CHD) and subjects with no history of CHD. Material and Methods: Participants were 161 patients (40-75) with severe angina pectoris (diagnosed as CHD by coronary angiography) who subsequently underwent percutaneous coronary intervention and 162 control subjects with no history of CHD. Periodontal status was recorded. Bone loss was determined on radiographs. Periodontal disease experience was classified into five groups according to Hugoson & Jordan. Results: Periodontal disease experience groups 4 and 5 were more common in the CHD group (25%) compared with the control group (8%). The mean bone level (the distance from the CEJ to the most coronal level of the alveolar bone) was 3.0±1.0 mm in CHD subjects and 2.6±0.8 mm in controls. CHD patients had significantly lower numbers of natural teeth, higher numbers of periodontal pockets 4-6-mm and higher bleeding on probing (%). In a stepwise regression analysis, the factor periodontal disease experience groups 4+5 gave an odds ratio of 5.74 (2.07-15.90) for having CHD after controlling for smoking and age. Conclusion: Severe periodontal disease expressed by several clinical and radiographic parameters was more prevalent among subjects with CHD than among controls. Analysis, the factor periodontal disease experience groups 4+5 gave an odds ratio of 5.74 (2.07-15.90) for having CHD after controlling for smoking and age. © 2008 Blackwell Munksgaard.
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