ArticleCardiovascular research2017
OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA-NF-κB pathway.
Article in Cardiovascular research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01679431 (Metabolic Determinants of the Progression of Aortic Stenosis - PROGRESSA Study), which is not on this map. Cited by 49 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Metabolic Determinants of the Progression of Aortic Stenosis - PROGRESSA Study
Who cites it
49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Oxidized Phospholipids and Calcific Aortic Valvular Disease.Journal of the American College of Cardiology · 2024Pooled it
- Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.Circulation · 2024Pooled it
- Predictive value of lipoprotein(a) in coronary artery calcification among asymptomatic cardiovascular disease subjects: A systematic review and meta-analysis.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2023Pooled it
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Exploring CACNA1H as a potential candidate biomarker for calcific aortic valve disease.iScience · 2026Article
- Article
- Sex-specific lipidomic signatures in aortic valve disease reflect differential fibro-calcific progression.Nature communications · 2025Article
- Lipoprotein(a) and panvascular disease.Lipids in health and disease · 2025Review
- Biomarkers of Calcification, Endothelial Injury, and Platelet-Endothelial Interaction in Patients with Aortic Valve Stenosis.International journal of molecular sciences · 2025Article
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Generation of New Knock-Out Mouse Strains ofInternational journal of molecular sciences · 2025Article
- Diabetes and calcific aortic valve disease: implications of glucose-lowering medication as potential therapy.Frontiers in pharmacology · 2025Review
- Diabetes and calcific aortic valve disease: controversy of clinical outcomes in diabetes after aortic valve replacement.Frontiers in endocrinology · 2025Review
- Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.BMC medicine · 2024Article
- Calcific aortic valve disease: mechanisms, prevention and treatment.Nature reviews. Cardiology · 2023Review
- Atherosclerosis Calcification: Focus on Lipoproteins.Metabolites · 2023Review
- Platelet membrane-coated alterbrassicene A nanoparticle inhibits calcification of the aortic valve by suppressing phosphorylation P65 NF-κB.Theranostics · 2023Article
- Mechanical injury accentuates lipid deposition in ApoEFrontiers in cardiovascular medicine · 2023Article
- Enduring Reactive Oxygen Species Emission Causes Aberrant Protein S-Glutathionylation Transitioning Human Aortic Valve Cells from a Sclerotic to a Stenotic Phenotype.Antioxidants & redox signaling · 2022Article
- A Novel LncRNA SNHG3 Promotes Osteoblast Differentiation Through BMP2 Upregulation in Aortic Valve Calcification.JACC. Basic to translational science · 2022Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsOxidatively modified lipoproteins may promote the development/progression of calcific aortic valve stenosis (CAVS). Oxidative transformation of low-density lipoprotein (OxLDL) generates lysophosphatidic acid (LPA), a lipid mediator that accumulates in mineralized aortic valves. LPA activates at least six different G protein-coupled receptors, which may play a role in the pathophysiology of CAVS. We hypothesized that LPA derived from OxLDL may promote a NF-κB signature that drives osteogenesis in the aortic valve. METHODS AND
resultsThe role of OxLDL-LPA was examined in isolated valve interstitial cells (VICs) and the molecular pathway was validated in human explanted aortic valves and in a mouse model of CAVS. We found that OxLDL-LPA promoted the mineralization and osteogenic transition of VICs through LPAR1 and the activation of a RhoA-NF-κB pathway. Specifically, we identified that RhoA/ROCK activated IκB kinase alpha, which promoted the phosphorylation of p65 on serine 536 (p65 pS536). p65 pS536 was recruited to the BMP2 promoter and directed an osteogenic program not responsive to the control exerted by the inhibitor of kappa B. In LDLR-/-/ApoB100/100/IGFII transgenic mice (IGFII), which develop CAVS under a high-fat and high-sucrose diet the administration of Ki16425, a Lpar1 blocker, reduced by three-fold the progression rate of CAVS and also decreased the osteogenic activity as measured with a near-infrared fluorescent probe that recognizes hydroxyapatite of calcium.
conclusionsOxLDL-LPA promotes an osteogenic program in the aortic valve through a LPAR1-RhoA/ROCK-p65 pS536 pathway. LPAR1 may represent a suitable target to prevent the progression of CAVS.
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Registered trials
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.