ABSTRACT: Dynamic Changes in the Expressions of Elastogenesis- and Elastinolysis-Associated Genes and Remodeling of the Elastin Network in Volume-Overloaded Heart
Project description:Background: In the remodeling process of the volume-overloaded heart, the extracellular matrix (ECM) may be dynamically modified to adapt to hemodynamic stress. We investigated the expression of ECM-related genes and modification of the elastin network in the remodeling process of the left ventricles (LVs) of rats with aortocaval fistulae. Methods and Findings: Gene array analysis identified 36 upregulated and 11 downregulated ECM-related genes during evolution from the compensated to the late decompensated phase. Ingenuity Pathway Analysis identified the formation of elastic fibers as an important biological function. Real-time PCR confirmed persistent upregulation of elastogenesis-associated genes, including elastin, lysyl oxidase, lysyl oxidase like-1, fibrillin 1, fibulin 2, versican and latent transforming growth factor beta binding protein 2 at various intervals. The expression levels and enzymatic activities of potent elastases, cathepsin S and cathepsin K increased during the early phase. Immunofluorescence confocal microscopy showed that the microstructure of the elastin network was preserved during the early phase, degraded during the compensated phase, partially repaired during the early decompensated phase, and reinforced during the late decompensated phase. Assessment of elastin concentrations in the LVs showed a consistent temporal pattern throughout the course. Conclusions: In the volume-overloaded heart, upregulation of potent elastases during the early phase and persistent upregulation of elastogenesis-related genes result in early degradation followed by repair and reinforcement of the elastin network of the LV. Remodeling of the elastin network may contribute to changes in the mechanical property of the volume-overloaded heart.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
Project description:The aim of this project is to use an integrated approach involving TMT labeling and LC-MS/MS to quantify the dynamic changes of the whole proteome of chondrocytes of Rattus norvegicus.
