Project description:Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity amongst individuals afflicted with vascular diseases. We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). Gene expression profiling identified no significant single gene differences between the two groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were pre-determined to survey each of nine biological systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches Experiment Overall Design: We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). To allow power calculations to be done, we performed microarray analysis on BOEC from 27 normal subjects of diverse ages. Gene expression profilings were obtained by using Affymetrix U133A chips
Project description:Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity amongst individuals afflicted with vascular diseases. We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). Gene expression profiling identified no significant single gene differences between the two groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were pre-determined to survey each of nine biological systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches Keywords: disease status analysis
Project description:Comparison of temporal gene expression profiles to identify genes/pathways changing during ageing. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
