ArticleJournal of cellular and molecular medicine2020
Divergent effects of canonical and non-canonical TGF-β signalling on mixed contractile-synthetic smooth muscle cell phenotype in human Marfan syndrome aortic root aneurysms.
Article in Journal of cellular and molecular medicine, 2020. 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, 36 citations in OpenAlex.
- TRPV4 is Associated with a Marfan Syndrome-Related Mechanosensitive Gene Program in Aortic Smooth Muscle Cells.Biochemical genetics · 2026Article
- Porphyromonas gingivalis Type 9 Secretion System Promotes Dysregulation of Vascular Smooth Muscle Cell Plasticity With Perturbed TGF-β/Smad Signaling.MicrobiologyOpen · 2025Article
- Loeys-Dietz syndrome subtypes exhibit distinct clinical behavior and aortic cellular transcriptomic profiles.JTCVS open · 2025Article
- Semaphorin 3A protects against thoracic aortic aneurysm dissection by suppressing aortic angiogenesis.Angiogenesis · 2025Article
- Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals.Journal of the American Heart Association · 2024Article
- Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.International journal of molecular sciences · 2024Review
- Article
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- SPINT2 is involved in the proliferation, migration and phenotypic switching of aortic smooth muscle cells: Implications for the pathogenesis of thoracic aortic dissection.Experimental and therapeutic medicine · 2023Article
- Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome.The Journal of thoracic and cardiovascular surgery · 2023Article
- Article
- Multi-omics in thoracic aortic aneurysm: the complex road to the simplification.Cell & bioscience · 2023Review
- TGF-beta signal transduction: biology, function and therapy for diseases.Molecular biomedicine · 2022Review
- How vascular smooth muscle cell phenotype switching contributes to vascular disease.Cell communication and signaling : CCS · 2022Review
- Embryologic Origin Influences Smooth Muscle Cell Phenotypic Modulation Signatures in Murine Marfan Syndrome Aortic Aneurysm.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.European journal of clinical investigation · 2022Review
- Advanced Glycation End Products Induce Atherosclerosis via RAGE/TLR4 Signaling Mediated-M1 Macrophage Polarization-Dependent Vascular Smooth Muscle Cell Phenotypic Conversion.Oxidative medicine and cellular longevity · 2022Article
- Impact of Notch3 Activation on Aortic Aneurysm Development in Marfan Syndrome.Journal of immunology research · 2022Article
- Article
- Vascular Smooth Muscle Cells in Aortic Aneurysm: From Genetics to Mechanisms.Journal of the American Heart Association · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Aortic root aneurysm formation is a cardinal feature of Marfan syndrome (MFS) and likely TGF-β driven via Smad (canonical) and ERK (non-canonical) signalling. The current study assesses human MFS vascular smooth muscle cell (SMC) phenotype, focusing on individual contributions by Smad and ERK, with Notch3 signalling identified as a novel compensatory mechanism against TGF-β-driven pathology. Although significant ERK activation and mixed contractile gene expression patterns were observed by traditional analysis, this did not directly correlate with the anatomic site of the aneurysm. Smooth muscle cell phenotypic changes were TGF-β-dependent and opposed by ERK in vitro, implicating the canonical Smad pathway. Bulk SMC RNA sequencing after ERK inhibition showed that ERK modulates cell proliferation, apoptosis, inflammation, and Notch signalling via Notch3 in MFS. Reversing Notch3 overexpression with siRNA demonstrated that Notch3 promotes several protective remodelling pathways, including increased SMC proliferation, decreased apoptosis and reduced matrix metalloproteinase activity, in vitro. In conclusion, in human MFS aortic SMCs: (a) ERK activation is enhanced but not specific to the site of aneurysm formation; (b) ERK opposes TGF-β-dependent negative effects on SMC phenotype; (c) multiple distinct SMC subtypes contribute to a 'mixed' contractile-synthetic phenotype in MFS aortic aneurysm; and (d) ERK drives Notch3 overexpression, a potential pathway for tissue remodelling in response to aneurysm formation.
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Registered trials
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