Proteomic Analysis and Sex-Specific Changes in Chronically Ischemic Swine Myocardium Treated with Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin.

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BACKGROUND: Although sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to improve cardiovascular outcomes in general, little is presently known about any sex-specific changes that may result from this therapy. We sought to investigate and quantify potential sex-specific changes seen with the SGLT-2 inhibitor canagliflozin (CAN) in a swine model of chronic myocardial ischemia.

STUDY DESIGN: Eighteen Yorkshire swine underwent left thoracotomy with placement of an ameroid constrictor. Two weeks post-op, swine were assigned to receive either control (F=5, M=5), or CAN 300 mg daily (F=4, M=4). Following five weeks of therapy, swine underwent myocardial functional measurements and myocardial tissue was sent for proteomic analysis.

RESULTS: Functional measurements showed increased cardiac output, stroke volume, ejection fraction, and ischemic myocardial flow at rest in CAN males compared to control males (all p

CONCLUSIONS: Males treated with CAN had significant improvements in cardiac function that were not observed in females. Moreover, CAN treatment in males was associated with significantly more changes in protein expression than in females. The increased proteomic changes seen in the male CAN group likely contributed to the more robust changes in cardiac function seen in males treated with CAN.




Medicine and Health Sciences




Department of Surgery, Fellows and Residents, Department of Surgery Residents

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