ArticlePloS one2011
Inhibitory role of Notch1 in calcific aortic valve disease.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 113 citations in OpenAlex.
- Integrated biomarker landscape for the early detection and management of calcific aortic valve disease.European journal of clinical investigation · 2026Review
- Macrophages in Calcific Aortic Valve Disease: Paracrine and Juxtacrine Disease Drivers.Biomolecules · 2024Review
- Review
- Low expression of Notch1 may be associated with acute myocardial infarction.Frontiers in cardiovascular medicine · 2024Article
- Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.International journal of molecular sciences · 2023Review
- Localized Prox1 Regulates Aortic Valve Endothelial Cell Diversity and Extracellular Matrix Stratification in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study.International journal of molecular sciences · 2022Article
- Role of oxidative stress in calcific aortic valve disease and its therapeutic implications.Cardiovascular research · 2022Review
- Uncoupling the Vicious Cycle of Mechanical Stress and Inflammation in Calcific Aortic Valve Disease.Frontiers in cardiovascular medicine · 2022Review
- Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis.Frontiers in cardiovascular medicine · 2022Article
- PTH-induced EndMT via miR-29a-5p/GSAP/Notch1 pathway contributed to valvular calcification in rats with CKD.Cell proliferation · 2021Article
- Inflammatory and Biomechanical Drivers of Endothelial-Interstitial Interactions in Calcific Aortic Valve Disease.Circulation research · 2021Review
- Midkine Prevents Calcification of Aortic Valve Interstitial CellsFrontiers in cell and developmental biology · 2021Article
- Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells.Frontiers in cardiovascular medicine · 2021Article
- NOTCH Signaling in Aortic Valve Development and Calcific Aortic Valve Disease.Frontiers in cardiovascular medicine · 2021Review
- Adding a "Notch" to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach.Frontiers in cell and developmental biology · 2021Review
- Novel loss of function mutation in NOTCH1 in a family with bicuspid aortic valve, ventricular septal defect, thoracic aortic aneurysm, and aortic valve stenosis.Molecular genetics & genomic medicine · 2020Article
- Aortic Valve Stenosis and Mitochondrial Dysfunctions: Clinical and Molecular Perspectives.International journal of molecular sciences · 2020Review
- DAPT, a potent Notch inhibitor regresses actively growing abdominal aortic aneurysm via divergent pathways.Clinical science (London, England : 1979) · 2020Article
- The Role of Secretase Pathway in Long-term Brain Inflammation and Cognitive Impairment in an Animal Model of Severe Sepsis.Molecular neurobiology · 2020Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.
Indexed as
Identifiers
What OpenQuestion holds
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.