ArticleExperimental cell research2012
Interstitial fluid flow and cyclic strain differentially regulate cardiac fibroblast activation via AT1R and TGF-β1.
Article in Experimental cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Arrhythmic Mitral Valve Prolapse as a Regional Stretch-Induced Cardiomyopathy with Fibro-Inflammatory Signature: A Conceptual Review.Journal of cardiovascular development and disease · 2026Review
- Interstitial fluid flow in an engineered human lymph node stroma model modulates T cell egress and stromal change.APL bioengineering · 2025Article
- Soft bioreactor systems: a necessary step toward engineered MSK soft tissue?Frontiers in robotics and AI · 2024Review
- Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.Nature biomedical engineering · 2023Article
- GPCRs and fibroblast heterogeneity in fibroblast-associated diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Review
- The Role of the Piezo1 Mechanosensitive Channel in Heart Failure.Current issues in molecular biology · 2023Review
- Culturing of Cardiac Fibroblasts in Engineered Heart Matrix Reduces Myofibroblast Differentiation but Maintains Their Response to Cyclic Stretch and Transforming Growth Factor β1.Bioengineering (Basel, Switzerland) · 2022Article
- Extracellular Fluid Flow Induces Shallow Quiescence Through Physical and Biochemical Cues.Frontiers in cell and developmental biology · 2022Article
- Article
- Channelling the Force to Reprogram the Matrix: Mechanosensitive Ion Channels in Cardiac Fibroblasts.Cells · 2021Review
- Does the Heart Want What It Wants? A Case for Self-Adapting, Mechano-Sensitive Therapies After Infarction.Frontiers in cardiovascular medicine · 2021Article
- Aqueous humor renin, angiotensin I, and angiotensin II activity in primary open-angle glaucoma.Arquivos brasileiros de oftalmologia · 2020Article
- Therapeutic Targets for the Treatment of Cardiac Fibrosis and Cancer: Focusing on TGF-β Signaling.Frontiers in cardiovascular medicine · 2020Review
- Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation.Advanced healthcare materials · 2019Article
- Mechanoregulation of Myofibroblast Fate and Cardiac Fibrosis.Advanced biosystems · 2018Article
- Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7.Scientific reports · 2016Article
- Local fluid transfer regulation in heart extracellular matrix.Journal of physiology and biochemistry · 2016Article
- Cardiac Fibrosis: The Fibroblast Awakens.Circulation research · 2016Review
- An approach to quantifying 3D responses of cells to extreme strain.Scientific reports · 2016Article
- Hepatocyte growth factor regulates the TGF-β1-induced proliferation, differentiation and secretory function of cardiac fibroblasts.International journal of molecular medicine · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cardiac fibroblasts are exposed to both cyclic strain and interstitial fluid flow in the myocardium. The balance of these stimuli is affected by fibrotic scarring, during which the fibroblasts transition to a myofibroblast phenotype. The present study investigates the mechanisms by which cardiac fibroblasts seeded in three-dimensional (3D) collagen gels differentiate between strain and fluid flow. Neonatal cardiac fibroblast-seeded 3D collagen gels were exposed to interstitial flow and/or cyclic strain and message levels of collagens type I and III, transforming growth factor β1 (TGF-β1), and α-smooth muscle actin (α-SMA) were assessed. Flow was found to significantly increase and strain to decrease expression of myofibroblast markers. Corresponding immunofluorescence indicated that flow and strain differentially regulated α-SMA protein expression. The effect of flow was inhibited by exposure to losartan, an angiotensin II type 1 receptor (AT1R) blocker, and by introduction of shRNA constructs limiting AT1R expression. Blocking of TGF-β also inhibited the myofibroblast transition, suggesting that flow-mediated cell signaling involved both AT1R and TGF-β1. Reduced smad2 phosphorylation in response to cyclic strain suggested that TGF-β is part of the mechanism by which cardiac fibroblasts differentiate between strain-induced and flow-induced mechanical stress. Our experiments show that fluid flow and mechanical deformation have distinct effects on cardiac fibroblast phenotype. Our data suggest a mechanism in which fluid flow directly acts on AT1R and causes increased TGF-β1 expression, whereas cyclic strain reduces activation of smad proteins. These results have relevance to the pathogenesis and treatment of heart failure.
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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.