Heart failure & cardiomyopathies
Effects of canagliflozin on human myocardial redox signalling: clinical implications
Authors' conclusion
We demonstrate for the first time that canagliflozin suppresses myocardial NADPH oxidase activity and improves NOS coupling via SGLT1/AMPK/Rac1 signalling, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium.
Study context
- Population
- Patients undergoing cardiac surgery (right atrial appendage biopsies); H9C2 and primary human cardiomyocytesStudy 2: 51 patients
- Participants
- 364 patients
- Comparison
- Canagliflozin vs no canagliflozin
Main finding
As reported in the abstract
- SGLT1 abundantly expressed in human atrial tissue and human cardiomyocytes (hCM), contrary to SGLT2
- Myocardial SGLT1 expression positively associated with O2.- production and pro-fibrotic, pro-inflammatory and wall stretch gene expression
- Canagliflozin reduced NADPH oxidase activity via AMP kinase (AMPK)/Rac1 signalling and improved nitric oxide synthase (NOS) coupling via increased tetrahydrobiopterin bioavailability ex vivo and in vitro
- Effects attenuated by SGLT1 knockdown in hCM
- Canagliflozin suppressed apoptotic and inflammatory pathways in hCM (ex vivo transcriptomics)
Original publication
Effects of canagliflozin on human myocardial redox signalling: clinical implications. Eur Heart J. Published 19 July 2021. doi:10.
Summarised from the published abstract; every number is checked against it