Cardiovascular disease represents the major cause of morbidity and mortality in patients worldwide. Hyperglycemia, increases the glucose flux via polyol pathway and the key enzyme in this pathway, aldose reductase serves as a major contributor for diabetes associated complications. Aldose reductase mediates the conversion of glucose to sorbitol utilizing NADPH. Transgenic mice overexpressing human AR (hAR) increases the susceptibility to ischemic/reperfusion injury as well as to atheroscelerotic lesions when fed with high fat diet.
We hypothesize that transgenic mice expressing human AR, creates epigenetic imprints, which then leads to its susceptibility to ischemic injury. My work focuses on the epigenetic changes induced by AR expression and how they contribute to lipotoxicity in heart tissues. Our data pinpoints the protein acetylation as a very important factor in inducing the lipotoxicity in tissues.
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2. Sowpati DT*, Thiagarajan D*, Sharma S, Sultana H, John R, Surani A, Mishra RK and Khosla S. An intronic DNA sequence within the mouse Neuronatin gene exhibits biochemical characteristics of an ICR and acts as a transcriptional activator in Drosophila. Mech. Dev. 2008, Nov-Dec; 125(11-12):963-73. *Co-first authors
To delineate the downstream effects of the protein acetylation changes caused by AR overexpression and to dissipate these negative changes by epigenetic modulators.