Abstract 4145779: Proteomic Insights into High-Fat Diet's Impact on Chronic Myocardial Ischemia in a Swine Model

Introduction: The effect of obesogenic diet on the outcomes of coronary artery disease are controversial with some clinical studies suggesting a paradoxical favorable effect of obesity. We seek to better understand the effects of high-fat diet on chronic myocardial ischemia using a swine model of chronic myocardial ischemia and Proteomic Analysis. Methods: Twenty 6-week-old Yorkshire swine received 5 weeks of normal diet (n=9, ND) or high-fat diet (n=11, HFD) prior to the placement of an ameroid constrictor on the left coronary circumflex artery to induce chronic myocardial ischemia. The swine continued ND or HFD for seven weeks after the procedure. At that time, the swine underwent terminal harvest with functional measurement and tissue collection for proteomic analysis. Results: There was a significant increase in ejection fraction, tau, myocardial perfusion, and PRSW in the HFD compared to ND (all p<0.05). There was no change in cardiac output (p=0.73). Proteomic analysis identified a total of 2,782 proteins. The HFD ischemic myocardium had 430 significantly increased and 105 significantly decreased proteins. The HFD non-ischemic group had 251 significantly increased and 94 significantly decreased proteins. Pathway analysis of the ischemic myocardium showed increases in pathways related to fatty acid metabolism and amino acid metabolism and decreases in pathways related to cytoskeletal structure in the HFD compared to ND. Pathway analysis of the non-ischemic myocardium also showed increases in pathways related to fatty acid metabolism and decreases in pathways related to cytoskeletal structure in the HFD compared to ND. Conclusions: HFD results in paradoxical increases in cardiac perfusion and function in the setting of chronic myocardial ischemia. This was accompanied by an increase in fatty acid metabolism and amino acid metabolism in both the ischemic and non-ischemic myocardium in the HFD compared to ND. There were decreases in several pathways related to cytoskeletal organization in the HFD compared to ND. This suggests that a high-fat diet may initially increase cardiac function through altered metabolism, but deteriorations in cytoskeletal structure may help explain longer-term complications.