ArticleCardiovascular research2023
Sodium-glucose cotransporter 2 inhibitor canagliflozin alleviates vascular calcification through suppression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 61 citations in OpenAlex.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- Canagliflozin regulates adipocyte lipolysis in vitro via a SGLT2 independent signaling pathway.International journal of obesity (2005) · 2026Article
- Vasculoprotective Effects of Sodium-Glucose Co-Transporter Inhibitors in Non-Diabetic Experimental Settings: A Narrative Review.International journal of molecular sciences · 2026Review
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- Differential expression of GLP1R, PCSK9, and SGLT2 in human aortic versus mitral valve tissues: exploratory findings in calcific aortic valve disease.Frontiers in cardiovascular medicine · 2026Article
- Chinese medicine and intermittent fasting integration therapy attenuate diabetic vascular calcificationActa pharmaceutica Sinica. B · 2026Article
- Medial arterial calcification in ageing and disease: current evidence and knowledge gaps.European heart journal · 2025Review
- Irisin targets the HK1-glycolysis-NLRP3 pyroptosis axis to prevent chronic kidney disease-associated vascular calcification.Renal failure · 2025Article
- The Impact of Sodium Glucose Co-Transporter 2 (SGLT-2) Inhibitors on Atherogenesis: A Systematic Review of Experimental and Clinical Evidence.Life (Basel, Switzerland) · 2025Review
- Oxidative-Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications.Current issues in molecular biology · 2025Review
- Shared Mechanisms in Cancer and Cardiovascular Disease: S100A8/9 and the NLRP3 Inflammasome: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- Tripeptide DT-109 (Gly-Gly-Leu) attenuates atherosclerosis and vascular calcification in nonhuman primates.Signal transduction and targeted therapy · 2025Article
- Anti-Inflammatory Effects of SGLT2 Inhibitors: Focus on Macrophages.International journal of molecular sciences · 2025Review
- Aortic Stenosis Prevention: Is a New Cardiovascular Disease Paradigm Coming of Age?Journal of clinical medicine · 2025Review
- Impact of sodium-glucose cotransporter-2 inhibitors on pulmonary vascular cell function and arterial remodeling.World journal of cardiology · 2025Review
- The lncRNA SENCR knockdown alleviates vascular calcification via miR-4731-5p by suppressing endoplasmic reticulum stress.PloS one · 2025Article
- Interleukin family in vascular calcification: molecular mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2025Review
- Immune mechanisms in chronic kidney disease-mineral and bone disorder: current insights and therapeutic implications.Frontiers in medicine · 2025Review
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsVascular calcification (VC) is prevalent in pathological processes such as diabetes, chronic kidney disease (CKD), and atherosclerosis, but effective therapies are still lacking by far. Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, has been approved for the treatment of type 2 diabetes mellitus and exhibits beneficial effects against cardiovascular disease. However, the effect of CANA on VC remains unknown. In this study, we hypothesize that CANA protects against VC. METHODS AND
resultsMicro-computed tomography analysis and alizarin red staining revealed that CANA treatment prevented aortic calcification in CKD rats and in VitD3-overloaded mice. Moreover, CANA alleviated the calcification of rat and human arterial rings. Alizarin red staining revealed that calcification of rat and human vascular smooth muscle cells (VSMCs) was attenuated by CANA treatment and this phenomenon was confirmed by calcium content assay. In addition, CANA downregulated the expression of osteogenic differentiation markers Runx2 and BMP2. Of interest, qPCR and western blot analysis revealed that CANA downregulated the expression of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and the downstream signalling molecules Caspase-1 and IL-1β in VSMCs as well. Both NLRP3 inhibitor MCC950 and knockdown of NLRP3 by siRNA independently resulted in decreased calcification of VSMCs. By contrast, activation of NLRP3 exacerbated VSMC calcification, and this effect was prevented by the addition of CANA.
conclusionsOur study for the first time demonstrates that CANA exerts a protective effect on VC at least partially via suppressing the NLRP3 signalling pathway. Therefore, supplementation of CANA as well as inhibition of NLRP3 inflammasome presents a potential therapy for VC.
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