ArticleThe Journal of clinical investigation2021
Thymosin β4 protects against aortic aneurysm via endocytic regulation of growth factor signaling.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Vascular Smooth Muscle Cell Plasticity in Atherosclerosis: Mechanisms, Recent Advances, and Therapeutic Implications.Reviews in cardiovascular medicine · 2026Review
- Research Progress on the Molecular Mechanism of LRP1 and TGFβ-PDGFRβ Signaling Network in Atherosclerosis and Vascular Remodeling.International journal of molecular sciences · 2026Review
- Accelerated biological aging, genetic susceptibility, and lifestyle in relation to abdominal aortic aneurysm: A prospective study.The journal of nutrition, health & aging · 2026Article
- Multifaceted role of nitric oxide in vascular dementia.Medical gas research · 2025Review
- Vascular Smooth Muscle Cell Metabolic Reprogramming in Arteriovenous Fistula Failure.Biomedicines · 2025Review
- Differential expression of PPARγ by pioglitazone and telmisartan causes effect of disparity on mTORC2-mediated cell proliferation and migration.Scientific reports · 2025Article
- HINT1 aggravates aortic aneurysm by targeting ITGA6/FAK axis in vascular smooth muscle cells.The Journal of clinical investigation · 2025Article
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- PDGF-BB/EGR1 Axis Drives Fibroblast Activation Protein Expression to Promote Abdominal Aortic Aneurysm.International journal of medical sciences · 2025Article
- Macrophage-derived KIF13B interacts with USP9X to attenuate abdominal aortic aneurysm development by potentiating TFEB stability.Theranostics · 2025Article
- Olfactory Receptors and Aortic Aneurysm: Review of Disease Pathways.Journal of clinical medicine · 2024Review
- SLC44A2 regulates vascular smooth muscle cell phenotypic switching and aortic aneurysm.The Journal of clinical investigation · 2024Article
- Small Spleen Peptides (SSPs) Shape Dendritic Cell Differentiation through Modulation of Extracellular ATP Synthesis Profile.Biomolecules · 2024Article
- Calcitonin Inhibits Phenotypic Switching of Aortic Smooth Muscle Cells and Neointimal Hyperplasia through the AMP-Activated Protein Kinase/Mechanistic Target of Rapamycin Pathway.ACS pharmacology & translational science · 2024Article
- The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.Acta pharmaceutica Sinica. B · 2024Article
- Epigenetic modifications in abdominal aortic aneurysms: from basic to clinical.Frontiers in cardiovascular medicine · 2024Review
- The anti-inflammatory and tolerogenic potential of small spleen peptides.Frontiers in immunology · 2024Review
- Clearance of Stress-Induced Premature Senescent Cells Alleviates the Formation of Abdominal Aortic Aneurysms.Aging and disease · 2023Article
- Article
- Protective Role for Smooth Muscle Cell Hepcidin in Abdominal Aortic Aneurysm.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic modulation which increases susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesized that Thymosin β4 (Tβ4) may function to maintain healthy vasculature throughout postnatal life. This was supported by the identification of an interaction with low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of platelet-derived growth factor BB (PDGF-BB) signaling and VSMC proliferation. LRP1 variants have been implicated by genome-wide association studies with risk of AAA and other arterial diseases. Tβ4-null mice displayed aortic VSMC and elastin defects that phenocopy those of LRP1 mutants, and their compromised vascular integrity predisposed them to Angiotensin II-induced aneurysm formation. Aneurysmal vessels were characterized by enhanced VSMC phenotypic modulation and augmented PDGFR-β signaling. In vitro, enhanced sensitivity to PDGF-BB upon loss of Tβ4 was associated with dysregulated endocytosis, with increased recycling and reduced lysosomal targeting of LRP1-PDGFR-β. Accordingly, the exacerbated aneurysmal phenotype in Tβ4-null mice was rescued upon treatment with the PDGFR-β antagonist Imatinib. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health, and provides insights into the mechanisms of growth factor-controlled VSMC phenotypic modulation underlying aortic disease progression.
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What Socratic holds
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 Socratic graph.