Effects of Extracellular Matrix Glycation on Cell and Tissue Function

Title: Effects of Extracellular Matrix Glycation on Cell and Tissue Function
Authors: Nadlacki, Borivoje Bora
Date: 2017
Abstract: Methylglyoxal (MG) is a reactive dicarbonyl derived as a by-product of glycolysis. If MG is not metabolized by glyoxalase-1 (Glo1), it glycates macromolecules producing advanced glycation end products (AGEs); these have been linked to larger infarct sizes and poorer cardiac function after myocardial infarction (MI). Proteins of the extracellular matrix (ECM) are prime targets for glycation by MG, but it is unknown if MG modification of the ECM may be a mechanism that contributes to the poor repair and function of the post-MI heart. This study sought to examine if MG-induced modifications of ECM proteins negatively affect fibroblast and endothelial cell function. Analysis with an MG-derived hydroimidazolone 1 (MG-H1) antibody confirmed MG modification of laminin and collagen type (Col) 1, 3, and 4. MG modifications decreased endothelial cell (EC) adhesion on Col3, Col4, and laminin and angiogenesis on ECMatrix. Furthermore, alpha smooth muscle actin staining indicated increased myofibroblast differentiation of fibroblasts on MG-modified proteins. Following induction of MI, extracted mouse hearts were decellularized and compared to healthy controls. Perhaps a result of technical challenges, both western blot and immunohistochemistry contrasted previous data by displaying a marked decrease in MG-H1 modifications post-MI. Overall, these results indicate that MG modifications of the ECM negatively influence EC and fibroblast function, requiring more research on their impact in cardiovascular disease progression.
URL: http://hdl.handle.net/10393/35806
CollectionThèses, 2011 - // Theses, 2011 -