ArticleBMC medicine2024
Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.
Article in BMC medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- Aortic valve disease: Novel animal models for advancing our understanding of the underlying mechanisms.Animal models and experimental medicine · 2026Review
- Article
- Calcific Aortopathy in Response to Aging and Injury.Circulation · 2026Review
- Targeting Tumor Necrosis Factor-α Mitigates Glucose Fluctuation-Induced Aortic Valve Fibrosis: Insights From Diabetic Rat Models.Reviews in cardiovascular medicine · 2026Article
- Precision RNA interference of Smad3 and Runx2 via dual targeting nanocarriers mitigates aortic valve disease.Journal of translational medicine · 2026Article
- Autotaxin-Scavenging Nanoliposomes for Prolonged Colon Retention and Autophagy-Mediated Mucosal Immune Restoration in Colitis.Biomaterials research · 2026Article
- Lipoprotein(a) and calcific aortic stenosis: from inherited risk marker to therapeutic target.Frontiers in medicine · 2026Review
- Deciphering the Enigma of Calcific Aortic Valve Disease: The Pivotal Role of Animal Models in Unraveling Pathogenesis and Advancing Therapeutic Strategies.Biomedicines · 2025Review
- Biomarkers of Calcification, Endothelial Injury, and Platelet-Endothelial Interaction in Patients with Aortic Valve Stenosis.International journal of molecular sciences · 2025Article
- Inhibition of lnc-COL6A1-6-Alleviated Osteogenic Differentiation of Valvular Interstitial Cells During Aortic Valve Calcification.Cardiovascular therapeutics · 2025Article
- Correction: Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.BMC medicine · 2024Article
- Myeloid-specific deletion of autotaxin inhibits rheumatoid arthritis and osteoclastogenesis.Frontiers in immunology · 2024Article
- The Combined Effect of the Systemic Immune-Inflammation Index and Aortic Valve Calcification on Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease.Journal of inflammation research · 2024Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPatients with fibro-calcific aortic valve disease (FCAVD) have lipid depositions in their aortic valve that engender a proinflammatory impetus toward fibrosis and calcification and ultimately valve leaflet stenosis. Although the lipoprotein(a)-autotaxin (ATX)-lysophosphatidic acid axis has been suggested as a potential therapeutic target to prevent the development of FCAVD, supportive evidence using ATX inhibitors is lacking. We here evaluated the therapeutic potency of an ATX inhibitor to attenuate valvular calcification in the FCAVD animal models.
methodsATX level and activity in healthy participants and patients with FCAVD were analyzed using a bioinformatics approach using the Gene Expression Omnibus datasets, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and western blotting. To evaluate the efficacy of ATX inhibitor, interleukin-1 receptor antagonist-deficient (Il1rn
resultsThe global gene expression profiles of the aortic valve tissue of patients with severe FCAVD demonstrated that ATX gene expression was significantly upregulated and correlated with lipid retention (r = 0.96) or fibro-calcific remodeling-related genes (r = 0.77) in comparison to age-matched non-FCAVD controls. Orally available ATX inhibitor, BBT-877, markedly ameliorated the osteogenic differentiation and further mineralization of primary human VICs in vitro. Additionally, ATX inhibition significantly attenuated fibrosis-related factors' production, with a detectable reduction of osteogenesis-related factors, in human VICs. Mechanistically, ATX inhibitor prohibited fibrotic changes in human VICs via both canonical and non-canonical TGF-β signaling, and subsequent induction of CTGF, a key factor in tissue fibrosis. In the in vivo FCAVD model system, ATX inhibitor exposure markedly reduced calcific lesion formation in interleukin-1 receptor antagonist-deficient mice (Il1rn
conclusionsATX inhibition attenuates the development of FCAVD while protecting against fibrosis and calcification in VICs, suggesting the potential of using ATX inhibitors to treat FCAVD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.