ArticleArteriosclerosis, thrombosis, and vascular biology2009
Statins block calcific nodule formation of valvular interstitial cells by inhibiting alpha-smooth muscle actin expression.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2009. 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 43 papers.
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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.
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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.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm.The Journal of pediatrics · 2019Trial
- In Vivo Three-Dimensional Geometric Reconstruction of the Mouse Aortic Heart Valve.Annals of biomedical engineering · 2024Article
- Predicting key gene related to immune infiltration and myofibroblast-like valve interstitial cells in patients with calcified aortic valve disease based on bioinformatics analysis.Journal of thoracic disease · 2023Article
- High resolution monitoring of valvular interstitial cell driven pathomechanisms in procalcific environment using label-free impedance spectroscopy.Frontiers in cardiovascular medicine · 2023Article
- Hyaluronic acid regulates heart valve interstitial cell contraction in fibrin-based scaffolds.Acta biomaterialia · 2021Article
- Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow.Biomedicines · 2021Article
- Tumor necrosis factor-α promotes and exacerbates calcification in heart valve myofibroblast populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Dissecting Calcific Aortic Valve Disease-The Role, Etiology, and Drivers of Valvular Fibrosis.Frontiers in cardiovascular medicine · 2021Review
- Organ Culture Model of Aortic Valve Calcification.Frontiers in cardiovascular medicine · 2021Article
- Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?Journal of materials science. Materials in medicine · 2020Review
- COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification.International journal of molecular sciences · 2020Article
- Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice.Current medical science · 2020Article
- Experimental Metabolic Syndrome Model Associated with Mechanical and Structural Degenerative Changes of the Aortic Valve.Scientific reports · 2018Article
- Simvastatin reduces the TLR4-induced inflammatory response in human aortic valve interstitial cells.The Journal of surgical research · 2018Article
- The Genetic Regulation of Aortic Valve Development and Calcific Disease.Frontiers in cardiovascular medicine · 2018Review
- Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification.Journal of the American Heart Association · 2017Review
- ADAMTS5 Deficiency in Calcified Aortic Valves Is Associated With Elevated Pro-Osteogenic Activity in Valvular Interstitial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Heart Valve Biomechanics and Underlying Mechanobiology.Comprehensive Physiology · 2016Review
- Surface chemistry regulates valvular interstitial cell differentiation in vitro.Acta biomaterialia · 2015Article
- Notch1 Mutation Leads to Valvular Calcification Through Enhanced Myofibroblast Mechanotransduction.Arteriosclerosis, thrombosis, and vascular biology · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveCalcific aortic stenosis, characterized by excessive fibrosis and deposition of bone-like calcified tissue, affects roughly 2% to 3% of the U.S. population over the age of 65. Recent studies have suggested that statins have a positive effect on the progression of aoritic stenosis, likely because of their ability to affect the resident cell population, known as valvular interstitial cells (VICs). VICs are fibroblastic cells that can differentiate to form activated myofibroblasts, displaying increased alpha smooth muscle actin (alphaSMA) expression, contractility, and collagen production. METHODS AND
resultsIn culture, VICs spontaneously form multicellular aggregates that subsequently develop into calcified nodules, providing an in vitro model for aortic stenosis. Using real-time microscopic tracking, we observed that confluent VIC monolayers spontaneously contract into rounded nodules, suggesting that myofibroblastic contractility is a critical step in the process of nodule formation. Overexpression of alphaSMA increased VIC calcific nodule formation and contractility, whereas knockdown of alphaSMA with siRNAs reduced these phenotypes, suggesting that the expression and contractile properties of alphaSMA are essential to the formation of nodules. Statin treatment of VICs reduced alphaSMA expression, inhibited contractility, and decreased nodule formation. When statins were used to treat preformed nodules, no decrease in the number of calcified nodules was observed, suggesting that statins may play more of a preventative role in aortic stenosis than a cure.
conclusionsOur studies provide evidence of a causal relationship between VIC myofibroblastic activity and initial VIC calcific nodule formation. Furthermore, we demonstrate that pravastatin inhibition of calcific nodule formation is related to inhibition of myofibroblastic activity.
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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.