ArticleScience translational medicine2019
Transcatheter aortic valve replacements alter circulating serum factors to mediate myofibroblast deactivation.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Circulating cytokines as triggers of endothelial dysfunction and sex-specific interstitial cell response in fibrocalcific aortic valve disease.International journal of biological sciences · 2026Article
- Fibroblast activation and heterogeneity in fibrotic disease.Nature reviews. Nephrology · 2025Review
- Determining sex differences in aortic valve myofibroblast responses to drug combinations identified using a digital medicine platform.Science advances · 2025Article
- Y chromosome-linked UTY modulates sex differences in valvular fibroblast methylation in response to nanoscale extracellular matrix cues.Science advances · 2025Article
- Engineering aortic valves via transdifferentiating fibroblasts into valvular endothelial cells without using viruses or iPS cells.Bioactive materials · 2025Article
- Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials.Journal of biomedical materials research. Part A · 2025Article
- Embracing sex-specific differences in engineered kidney models for enhanced biological understanding of kidney function.Biology of sex differences · 2024Review
- Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation.Matrix biology plus · 2024Article
- Substrate stiffness modulates cardiac fibroblast activation, senescence, and proinflammatory secretory phenotype.American journal of physiology. Heart and circulatory physiology · 2024Article
- Albumin Thiolation and Oxidative Stress Status in Patients with Aortic Valve Stenosis.Biomolecules · 2023Article
- Aortic Stenosis Phenotypes and Precision Transcatheter Aortic Valve Implantation.Journal of cardiovascular development and disease · 2023Review
- Sex as a Biological Variable in Tissue Engineering and Regenerative Medicine.Annual review of biomedical engineering · 2023Review
- Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.European heart journal · 2023Article
- Roadmap on biomaterials for women's health.JPhys materials · 2023Article
- Osteopontin activity modulates sex-specific calcification in engineered valve tissue mimics.Bioengineering & translational medicine · 2023Article
- Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation.Biomaterials science · 2022Article
- Chemical and molecular tools to probe biological sex differences at multiple length scales.Journal of materials chemistry. B · 2022Review
- Hydrogel cultures reveal Transient Receptor Potential Vanilloid 4 regulation of myofibroblast activation and proliferation in valvular interstitial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Creating a science legacy.Nature · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The transcatheter aortic valve replacement (TAVR) procedure has emerged as a minimally invasive treatment for patients with aortic valve stenosis (AVS). However, alterations in serum factor composition and biological activity after TAVR remain unknown. Here, we quantified the systemic inflammatory effects of the TAVR procedure and hypothesized that alterations in serum factor composition would modulate valve and cardiac fibrosis. Serum samples were obtained from patients with AVS immediately before their TAVR procedure (pre-TAVR) and about 1 month afterward (post-TAVR). Aptamer-based proteomic profiling revealed alterations in post-TAVR serum composition, and ontological analysis identified inflammatory macrophage factors implicated in myofibroblast activation and deactivation. Hydrogel biomaterials used as valve matrix mimics demonstrated that post-TAVR serum reduced myofibroblast activation of valvular interstitial cells relative to pre-TAVR serum from the same patient. Transcriptomics and curated network analysis revealed a shift in myofibroblast phenotype from pre-TAVR to post-TAVR and identified p38 MAPK signaling as one pathway involved in pre-TAVR-mediated myofibroblast activation. Post-TAVR serum deactivated valve and cardiac myofibroblasts initially exposed to pre-TAVR serum to a quiescent fibroblast phenotype. Our in vitro deactivation data correlated with patient disease severity measured via echocardiography and multimorbidity scores, and correlations were dependent on hydrogel stiffness. Sex differences in cellular responses to male and female sera were also observed and may corroborate clinical observations regarding sex-specific TAVR outcomes. Together, alterations in serum composition after TAVR may lead to an antifibrotic fibroblast phenotype, which suggests earlier interventions may be beneficial for patients with advanced AVS to prevent further disease progression.
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Registered trials
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