ArticleAntioxidants (Basel, Switzerland)2022
Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- Effect of Peroxynitrite on Endothelial-Mesenchymal Transition Markers in Primary Endothelial Cell Cultures In Vitro.Bulletin of experimental biology and medicine · 2026Article
- 3D Contractile and Remodeling Behaviors of Functionally Normal and Prolapsed Human Mitral Valve Interstitial Cells.Annals of biomedical engineering · 2026Article
- ILK-Dependent Modulation of DPP4 Prevents Progression of Calcific Aortic Valve Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Endothelial Integrin-Linked Kinase (ILK) Deficiency Promotes Endothelial Activation and Cardiovascular Dysfunction via Receptor Interacting Protein Kinase-1 (RIPK1) Enriched-Extracellular Vesicle Signalling.Journal of extracellular vesicles · 2026Article
- Shared pathophysiological mechanisms between diabetes and calcific aortic valve disease: an immunometabolic perspective.Cardiovascular diabetology · 2026Review
- Calcific aortic valve disease: can targeting endothelial-mesenchymal transition be a new alternative to surgery?-a narrative review.Cardiovascular diagnosis and therapy · 2026Review
- Integrated biomarker landscape for the early detection and management of calcific aortic valve disease.European journal of clinical investigation · 2026Review
- Extracellular Vesicles in Calcific Aortic Valve Disease: From Biomarkers to Drug Delivery Applications.Biomolecules · 2025Review
- 3D Contractile and Remodeling Behaviors of Functionally Normal and Prolapsed Human Mitral Valve Interstitial Cells.bioRxiv : the preprint server for biology · 2025Article
- Article
- Plasma Cell-Free DNA Is a Potential Biomarker for Diagnosis of Calcific Aortic Valve Disease.Cardiology · 2024Article
- Niclosamide Inhibits Aortic Valve Interstitial Cell Calcification by Interfering with the GSK-3β/β-Catenin Signaling Pathway.Biomolecules & therapeutics · 2023Article
- Focusing on the Native Matrix Proteins in Calcific Aortic Valve Stenosis.JACC. Basic to translational science · 2023Review
- Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition.Basic research in cardiology · 2023Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Calcific aortic valve disease (CAVD) is highly prevalent during aging. CAVD initiates with endothelial dysfunction, leading to lipid accumulation, inflammation, and osteogenic transformation. Integrin-linked kinase (ILK) participates in the progression of cardiovascular diseases, such as endothelial dysfunction and atherosclerosis. However, ILK role in CAVD is unknown. First, we determined that ILK expression is downregulated in aortic valves from patients with CAVD compared to non-CAVD, especially at the valve endothelium, and negatively correlated with calcification markers. Silencing ILK expression in human valve endothelial cells (siILK-hVECs) induced endothelial-to-mesenchymal transition (EndMT) and promoted a switch to an osteoblastic phenotype; SiILK-hVECs expressed increased RUNX2 and developed calcified nodules. siILK-hVECs exhibited decreased NO production and increased nitrosative stress, suggesting valvular endothelial dysfunction. NO treatment of siILK-hVECs prevented VEC transdifferentiation, while treatment with an eNOS inhibitor mimicked ILK-silencing induction of EndMT. Accordingly, NO treatment inhibited VEC calcification. Mechanistically, siILK-hVECs showed increased Smad2 phosphorylation, suggesting a TGF-β-dependent mechanism, and NO treatment decreased Smad2 activation and RUNX2. Experiments performed in eNOS KO mice confirmed the involvement of the ILK-eNOS signaling pathway in valve calcification, since aortic valves from these animals showed decreased ILK expression, increased RUNX2, and calcification. Our study demonstrated that ILK endothelial expression participates in human CAVD development by preventing endothelial osteogenic transformation.
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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 Socratic graph.