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• W2896977034 abstract "Elastic fibers provide reversible elasticity to the large arteries and are assembled during development when hemodynamic forces are increasing. Mutations in elastic fiber genes are associated with cardiovascular disease. Mice lacking expression of the elastic fiber genes elastin ( Eln −/− ), fibulin-4 ( Efemp2 −/− ), or lysyl oxidase ( Lox −/− ) die at birth with severe cardiovascular malformations. All three genetic knockout models have elastic fiber defects, aortic wall thickening, and arterial tortuosity. However, Eln −/− mice develop arterial stenoses, while Efemp2 −/− and Lox −/− mice develop ascending aortic aneurysms. We performed comparative gene array analyses of these three genetic models for two vascular locations and developmental stages to determine differentially expressed genes and pathways that may explain the common and divergent phenotypes. We first examined arterial morphology and wall structure in newborn mice to confirm that the lack of elastin, fibulin-4, or lysyl oxidase expression provided the expected phenotypes. We then compared gene expression levels for each genetic model by three-way ANOVA for genotype, vascular location, and developmental stage. We found three genes upregulated by genotype in all three models, Col8a1, Igfbp2, and Thbs1, indicative of a common response to severe elastic fiber defects in developing mouse aorta. Genes that are differentially regulated by vascular location or developmental stage in all three models suggest mechanisms for location or stage-specific disease pathology. Comparison of signaling pathways enriched in all three models shows upregulation of integrins and matrix proteins involved in early wound healing, but not of mature matrix molecules such as elastic fiber proteins or fibrillar collagens." @default.
• W2896977034 created "2018-10-26" @default.
• W2896977034 creator A5007156575 @default.
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• W2896977034 creator A5047673091 @default.
• W2896977034 creator A5078623638 @default.
• W2896977034 creator A5080025502 @default.
• W2896977034 date "2018-11-01" @default.
• W2896977034 modified "2023-10-14" @default.
• W2896977034 title "Comparative gene array analyses of severe elastic fiber defects in late embryonic and newborn mouse aorta" @default.
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