ArticleScientific reports2021
Canagliflozin protects against sepsis capillary leak syndrome by activating endothelial α1AMPK.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial.The lancet. Diabetes & endocrinology · 2024Trial
- Safety and clinical impact of SGLT2 inhibitor in patients undergoing peritoneal dialysis: a target-trial emulation study.Clinical kidney journal · 2026Article
- Sodium-glucose cotransporter-2 inhibitors and sepsis: a story with two tails or with one tail?Inflammopharmacology · 2026Review
- Capillary leak syndrome in sepsis: the role of intrinsic coagulation pathway activation.BMC infectious diseases · 2025Article
- Association between the nutritional inflammation index and mortality among patients with sepsis: insights from traditional methods and machine learning-based mortality prediction.BMC infectious diseases · 2025Article
- Impact of sodium-glucose cotransporter-2 inhibitors on pulmonary vascular cell function and arterial remodeling.World journal of cardiology · 2025Review
- Are sodium-glucose co-transporter-2 inhibitors associated with improved outcomes in diabetic patients admitted to intensive care units with septic shock?Acute and critical care · 2024Article
- Vascular leak in sepsis: physiological basis and potential therapeutic advances.Critical care (London, England) · 2024Review
- Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy.Cardiovascular research · 2023Review
- PCSK9 Promotes Endothelial Dysfunction During Sepsis Via the TLR4/MyD88/NF-κB and NLRP3 Pathways.Inflammation · 2023Article
- Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function.Drug design, development and therapy · 2022Review
- The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction FollowingInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis capillary leak syndrome (SCLS) is an independent prognostic factor for poor sepsis outcome. We previously demonstrated that α1AMP-activated protein kinase (α1AMPK) prevents sepsis-induced vascular hyperpermeability by mechanisms involving VE-cadherin (VE-Cad) stabilization and activation of p38 mitogen activated protein kinase/heat shock protein of 27 kDa (p38MAPK/HSP27) pathway. Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, has recently been proven to activate AMPK in endothelial cells. Therefore, we hypothesized that canagliflozin could be of therapeutic potential in patients suffering from SCLS. We herein report that canagliflozin, used at clinically relevant concentrations, counteracts lipopolysaccharide-induced vascular hyperpermeability and albumin leakage in wild-type, but not in endothelial-specific α1AMPK-knockout mice. In vitro, canagliflozin was demonstrated to activate α1AMPK/p38MAPK/HSP27 pathway and to preserve VE-Cad's integrity in human endothelial cells exposed to human septic plasma. In conclusion, our data demonstrate that canagliflozin protects against SCLS via an α1AMPK-dependent pathway, and lead us to consider novel therapeutic perspectives for this drug in SCLS.
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