ArticleThe Annals of thoracic surgery2011
Aortic valve cyclic stretch causes increased remodeling activity and enhanced serotonin receptor responsiveness.
Article in The Annals of thoracic surgery, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Inhibition of the serotonin transporter and risk of heart valve disease: A systematic review and meta-analysis.European journal of pharmacology · 2026Pooled it
- Drug-associated valvular heart diseases and serotonin-related pathways: a meta-analysis.Heart (British Cardiac Society) · 2019Pooled it
- From biomechanical mechanisms to clinical reasoning: Deciphering mechanobiological drivers of aortic valve calcification for precision therapy.Mechanobiology in medicine · 2026Review
- Selective right heart valve remodelling in a mouse model of carcinoid disease revealed by high-resolution episcopic microscopy.Scientific reports · 2025Article
- Bioinformatic analysis of potential biomarkers and mechanisms of immune infiltration in mitral regurgitation complicated by atrial fibrillation.Annals of translational medicine · 2022Article
- Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis.Circulation research · 2021Review
- On Valve Interstitial Cell Signaling: The Link Between Multiscale Mechanics and Mechanobiology.Cardiovascular engineering and technology · 2021Review
- Risk factors for valvular calcification.Current opinion in endocrinology, diabetes, and obesity · 2019Review
- The role of fibroblast growth factor 1 and 2 on the pathological behavior of valve interstitial cells in a three-dimensional mechanically-conditioned model.Journal of biological engineering · 2019Article
- The role of 5-HTBritish journal of pharmacology · 2017Article
- Serotonin and catecholamines in the development and progression of heart valve diseases.Cardiovascular research · 2017Article
- Mechanotransduction Mechanisms in Mitral Valve Physiology and Disease Pathogenesis.Frontiers in cardiovascular medicine · 2017Review
- Valve interstitial cell tensional homeostasis directs calcification and extracellular matrix remodeling processes via RhoA signaling.Biomaterials · 2016Article
- Manipulation of valve composition to elucidate the role of collagen in aortic valve calcification.BMC cardiovascular disorders · 2014Article
- Molecular and cellular aspects of calcific aortic valve disease.Circulation research · 2013Review
- Aortic valve: mechanical environment and mechanobiology.Annals of biomedical engineering · 2013Review
- Associations of LV hypertrophy with prevalent and incident valve calcification: Multi-Ethnic Study of Atherosclerosis.JACC. Cardiovascular imaging · 2012Article
- Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Comparative pathology of human and canine myxomatous mitral valve degeneration: 5HT and TGF-β mechanisms.Cardiovascular pathology : the official journal of the Society for Cardiovascular PathologyReview
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIncreased serotonin (5-hydroxytryptamine [5HT]) receptor (5HTR) signaling has been associated with cardiac valvulopathy. Prior cell culture studies of 5HTR signaling in heart valve interstitial cells have provided mechanistic insights concerning only static conditions. We investigated the hypothesis that aortic valve biomechanics participate in the regulation of both 5HTR expression and interrelated extracellular matrix remodeling events.
methodsThe effects of cyclic stretch on aortic valve 5HTR, expression, signaling, and extracellular matrix remodeling were investigated using a tensile stretch bioreactor in studies which also compared the effects of adding 5HT and (or) the 5HT-transporter inhibitor, fluoxetine.
resultsCyclic stretch alone increased both proliferation and collagen in porcine aortic valve cusp samples. However, with cyclic stretch, unlike static conditions, 5HT plus fluoxetine caused the greatest increase in proliferation (p<0.0001), and also caused significant increases in collagen (p<0.0001) and glycosaminoglycans (p<0.0001). The DNA microarray data demonstrated upregulation of 5HTR2A and 5HTR2B (>4.5-fold) for cyclic stretch versus static (p<0.001), while expression of the 5HT transporter was not changed significantly. Extracellular matrix genes (eg, collagen types I, II, III, and proteoglycans) were also upregulated by cyclic stretch.
conclusionsPorcine aortic valve cusp samples subjected to cyclic stretch upregulate 5HTR2A and 2B, and also initiate remodeling activity characterized by increased proliferation and collagen production. Importantly, enhanced 5HTR responsiveness due to increased 5HTR2A and 2B expression results in a significantly greater response in remodeling endpoints (proliferation, collagen, and GAG production) to 5HT in the presence of 5HT transporter blockade.
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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.