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Lipidomics of Health and Disease | EK30


Lipidomic Signature of Atrial Tissue Differentiates Diabetic from Non-Diabetic Coronary Artery Bypass Graft Patients


Mar 24, 2021 12:00am ‐ Mar 24, 2021 12:00am

Description

Lipidomic Signature of Atrial Tissue Differentiates Diabetic from Non-Diabetic Coronary Artery Bypass Graft Patients Ilka M. Pinz Ph.D.1, Michael Robich M.D.2, Douglas B. Sawyer M.D., Ph.D.1, 2, Calvin Vary Ph.D.1 Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 1; Department of Cardiac Services, Maine Medical Center, Portland, ME2 Diabetes mellitus is an important risk factor for acute myocardial infarction and chronic ischemic heart disease. While we are beginning to implicate some disease mechanisms on the RNA and protein levels, the role of cellular membrane lipids is not well investigated in human heart disease. We tested whether diabetic and non-diabetic coronary artery bypass grafting (CABG) patients have a distinguishable lipidomic signature, which we hypothesize may contribute to disrupted membrane lipid homeostasis. While we analyzed the global lipidome, we specifically investigated lipids associated with the caveolae membrane microdomain. The protocol and use of human tissue samples for this study has been approved by the Institutional Review Board of Maine Medical Center. To test our hypothesis, we used an unbiased mass spectrometric lipidomics approach (MS/MSAll) to determine the lipid profiles in right atrial appendix (RAA) tissue and blood plasma, and determined the expression of caveolin-1 and -3 in RAA by Western blotting. Lipidomic class enrichment ontological relationships were analyzed using the LION web tool. We found significantly different lipidomic signatures in diabetic vs. non-diabetic blood plasma and right atrial appendage tissue. A more detailed analysis showed that diabetic subjects have diminished lipid species that are required for positive and negative membrane curvatures, which are required for caveolae membrane microdomain organization. The expression of caveolin proteins varied throughout our patient population (n = 8), however was linearly correlated with the ratio of unsaturated to saturated sphingomyelin. These data support our hypothesis that dysregulated lipid homeostasis in cardiac cell membranes of diabetic patients may be contributing to the disease phenotype. Funding support: Pilot Project from the Cardiovascular Research Institute at Maine Medical Center

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