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Updated: Sep 18, 2025

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
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Sodium-Glucose Cotransporter 2 Inhibitors Preceding ST-Segment Elevation Myocardial Infarction: Global Proteomics and

Jay S Shavadia1, Megan Tomilin2, Paulos Chumala3

  • 1Department of Medicine, Division of Cardiology, College of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.

JACC. Advances
|June 24, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransport 2 receptor inhibitors (SGLT2i) may improve heart attack outcomes by up-regulating proteins involved in heme-scavenging and nitric oxide transport, potentially reducing infarct size.

Area of Science:

  • Cardiology
  • Proteomics
  • Pharmacology

Background:

  • Sodium-glucose cotransport 2 receptor inhibitors (SGLT2i) are known to improve cardiovascular outcomes post-myocardial infarction.
  • Limited research exists on the specific pathophysiological mechanisms influenced by SGLT2i prior to myocardial infarction.

Purpose of the Study:

  • To investigate differential protein regulation in patients with ST-segment elevation myocardial infarction (STEMI) who were taking SGLT2 inhibitors versus those who were not.
  • To identify specific protein markers associated with SGLT2 inhibitor use preceding STEMI.

Main Methods:

  • Blood samples were collected from STEMI patients between June 2021 and October 2023.
  • Propensity-matched pairs of diabetic patients on (SGLT2i+) and not on (SGLT2i-) SGLT2 inhibitors prior to STEMI were created.
  • Liquid chromatography-tandem mass spectrometry was used to identify differentially expressed proteins between the two groups.

Main Results:

  • Of 149 eligible diabetic STEMI patients, 33 propensity-matched pairs (SGLT2i+ vs. SGLT2i-) were analyzed.
  • Twenty-one differentially expressed proteins were identified between the groups.
  • Patients on SGLT2i+ showed a predominant up-regulation of proteins involved in heme-scavenging and nitric oxide transport compared to SGLT2i- patients.

Conclusions:

  • SGLT2 inhibitor use is associated with the up-regulation of heme-scavenging and nitric oxide-related proteins preceding STEMI.
  • This protein regulation may contribute to the observed reduction in infarct size and improved outcomes in heart failure post-myocardial infarction.
Keywords:
SGLT2iSTEMImass spectrometry-based proteomicsserum proteomics profiling

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