Sodium-Glucose Cotransporter-2 Canagliflozin's Impact on Cardiovascular Disease in the Setting of Metabolic Syndrome: A Proteomic Analysis.

Publication/Presentation Date

7-17-2025

Abstract

RATIONALE: Ischemic heart disease (IHD) is the leading cause of global mortality and is often complicated by metabolic syndrome (MetS), making its management challenging. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, such as canagliflozin (CAN), have demonstrated cardioprotective effects, but the precise molecular mechanisms underlying these benefits in the setting of IHD and MetS remain unclear.

OBJECTIVES: This study aimed to investigate the myocardial phenotypic changes induced by CAN treatment using a highly sensitive proteomic approach in a large animal model of IHD and MetS.

FINDINGS: In a swine model of MetS and chronic myocardial ischemia, CAN treatment led to significant metabolic shifts, including the downregulation of glycolysis and gluconeogenesis and the upregulation of oxidative phosphorylation and electron transport chain activity. Proteomic analysis revealed increased expression of vesicular and mitochondrial transport proteins in chronically ischemic myocardium and elevated thioredoxin levels in non-ischemic myocardium, indicating improved mitochondrial function, reduced oxidative stress, and enhanced cytoskeletal remodeling.

CONCLUSIONS: CAN treatment induces extensive myocardial adaptations that contribute to its cardioprotective effects, particularly by optimizing myocardial metabolism, mitigating oxidative stress, and promoting ventricular remodeling. These findings provide valuable insights into the therapeutic potential of CAN in IHD and MetS and highlight the utility of proteomics in advancing heart failure treatment strategies.

First Page

177975

Last Page

177975

ISSN

1879-0712

Disciplines

Medicine and Health Sciences

PubMedID

40683440

Department(s)

Fellows and Residents

Document Type

Article

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