ArticleHuman molecular genetics2021
Molecular phenotyping and functional assessment of smooth muscle-like cells with pathogenic variants in aneurysm genes ACTA2, MYH11, SMAD3 and FBN1.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 13 citations in OpenAlex.
- Ultrasound-Mediated OFF-to-ON Switching of Bone Regeneration via a Bioorthogonal Cell-Capture Hydrogel, Enabling Spatiotemporal Control and Monitoring.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure.Scientific reports · 2025Article
- Thoracic aortic aneurysm combined with intracranial vascular abnormalities caused by dual mutations inFrontiers in genetics · 2025Article
- ACTN2, regulated by PRDM9, affects the growth and inflammation of vascular smooth muscle cells by interacting with PDLIM1 in intracranial aneurysms.Frontiers in molecular neuroscience · 2025Article
- Functional analysis of cell lines derived from SMAD3-related Loeys-Dietz syndrome patients provides insights into genotype-phenotype relation.Human molecular genetics · 2024Article
- Genetic models of fibrillinopathies.Genetics · 2024Review
- The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.European journal of clinical investigation · 2022Review
- Single-cell RNA-seq reveals the communications between extracellular matrix-related components and Schwann cells contributing to the earlobe keloid formation.Frontiers in medicine · 2022Article
- Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance.Frontiers in genetics · 2022Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aortic aneurysms (AAs) are pathological dilatations of the aorta. Pathogenic variants in genes encoding for proteins of the contractile machinery of vascular smooth muscle cells (VSMCs), genes encoding proteins of the transforming growth factor beta signaling pathway and extracellular matrix (ECM) homeostasis play a role in the weakening of the aortic wall. These variants affect the functioning of VSMC, the predominant cell type in the aorta. Many variants have unknown clinical significance, with unknown consequences on VSMC function and AA development. Our goal was to develop functional assays that show the effects of pathogenic variants in aneurysm-related genes. We used a previously developed fibroblast transdifferentiation protocol to induce VSMC-like cells, which are used for all assays. We compared transdifferentiated VSMC-like cells of patients with a pathogenic variant in genes encoding for components of VSMC contraction (ACTA2, MYH11), transforming growth factor beta (TGFβ) signaling (SMAD3) and a dominant negative (DN) and two haploinsufficient variants in the ECM elastic laminae (FBN1) to those of healthy controls. The transdifferentiation efficiency, structural integrity of the cytoskeleton, TGFβ signaling profile, migration velocity and maximum contraction were measured. Transdifferentiation efficiency was strongly reduced in SMAD3 and FBN1 DN patients. ACTA2 and FBN1 DN cells showed a decrease in SMAD2 phosphorylation. Migration velocity was impaired for ACTA2 and MYH11 cells. ACTA2 cells showed reduced contractility. In conclusion, these assays for showing effects of pathogenic variants may be promising tools to help reclassification of variants of unknown clinical significance in AA-related genes.
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