ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
Tumor necrosis factor-α promotes and exacerbates calcification in heart valve myofibroblast populations.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Compensatory Mitophagy via NEDD4/HIF-1α/BNIP3 Pathway Restrains EndMT and Renal Allograft Interstitial Fibrosis Induced by TNFα.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effects of TNF-Journal of clinical medicine · 2026Article
- Inflammatory and hormonal crosstalk linking rheumatic fever to chronic valvular heart disease.Molecular biology reports · 2026Review
- NETs accelerate aortic valve calcification by promoting M1 macrophage polarization through the TLR9 signaling pathway.Molecular and cellular biochemistry · 2025Article
- Shared Risk Factors and Molecular Mechanisms Between Aortic Stenosis and Atherosclerosis: A Rationale for Therapeutic Repositioning.International journal of molecular sciences · 2025Review
- Lipoprotein(a) and panvascular disease.Lipids in health and disease · 2025Review
- Advances in Pathophysiological Mechanisms of Degenerative Aortic Valve Disease.Cardiology research · 2025Review
- Establishment and characterization of a novel immortalized human aortic valve interstitial cell line.Scientific reports · 2025Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
- Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis.Journal of translational medicine · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
- The role of macrophages in vascular calcification: strategies for diagnosis and treatment.Frontiers in immunology · 2025Review
- An overview of the application and potential mechanism on the triglyceride glucose index with multi-vessel coronary disease.Lipids in health and disease · 2024Review
- The Exacerbating Effects of the Tumor Necrosis Factor in Cardiovascular Stenosis: Intimal Hyperplasia.Cancers · 2024Review
- Active Ingredients and Mechanism of Gegen Qinlian Decoction in the Treatment of Diabetic Cardiomyopathy: A Network Pharmacology Study.Current pharmaceutical design · 2024Article
- Supplement of exogenous inorganic pyrophosphate inhibits atheromatous calcification in Apolipoprotein E knockout mice.Heliyon · 2023Article
- 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
- M1-Type Macrophages Secrete TNF-α to Stimulate Vascular Calcification by Upregulating CA1 and CA2 Expression in VSMCs.Journal of inflammation research · 2023Article
- 4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pro-inflammatory cytokines play critical roles in regulating valvular interstitial cell (VIC) phenotypic changes that can cause heart valve fibrosis and calcification. Tumor necrosis factor alpha (TNF-α) is a cytokine known to influence VIC behavior and has been reported at high levels in calcified valves ex vivo. We sought to understand the specific effects of TNF-α on VIC phenotypes (eg, fibroblast, profibrotic activated myofibroblasts) and its link with heart valve disorders. We characterize human aortic valve tissue from patients with valve disorders and identify a high variability of fibrotic and calcific markers between tissues. These results motivated in vitro studies to explore the effects of TNF-α on defined VIC fibroblasts and profibrotic activated myofibroblasts, induced via FGF-2 and TGF-β1 treatment. Using 3D hydrogels to culture VICs, we measure the effect of TNF-α (0.1-10 ng/mL) on key markers of fibrosis (eg, αSMA, COL1A1) and calcification (eg, RUNX2, BMP2, and calcium deposits). We observe calcification in TNF-α-treated VIC activated myofibroblasts and identify the MAPK/ERK signaling cascade as a potential pathway for TNF-α mediated calcification. Conversely, VIC fibroblasts respond to TNF-α with decreased calcification. Treatment of VIC profibrotic activated myofibroblast populations with TNF-α leads to increased calcification. Our in vitro findings correlate with findings in diseased human valves and highlight the importance of understanding the effect of cytokines and signaling pathways on specific VIC phenotypes. Finally, we reveal MAPK/ERK as a potential pathway involved in VIC-mediated matrix calcification with TNF-α treatment, suggesting this pathway as a potential pharmaceutical target for aortic valve disease.
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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.