ArticleArteriosclerosis, thrombosis, and vascular biology2018
FOXO3a (Forkhead Transcription Factor O Subfamily Member 3a) Links Vascular Smooth Muscle Cell Apoptosis, Matrix Breakdown, Atherosclerosis, and Vascular Remodeling Through a Novel Pathway Involving MMP13 (Matrix Metalloproteinase 13).
Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Rare-Earth Nanomaterials for Advanced Theranostics of Atherosclerosis.Chemical & biomedical imaging · 2026Review
- PCSK9 promotes atherosclerosis progression through the FOXO3a autophagy signaling pathway.Frontiers in cardiovascular medicine · 2026Article
- Vascular Smooth Muscle Cells: A Therapeutic Target in Atherosclerosis.Reviews in cardiovascular medicine · 2025Review
- Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins.Cardiovascular research · 2025Article
- Colchicine reduces neointima formation and VSMC phenotype transition by modulating SRF-MYOCD activation and autophagy.Acta pharmacologica Sinica · 2025Article
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-Aged Men: Kuakini Honolulu Heart Program.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Involvement of Kindlin-1 in cutaneous squamous cell carcinoma.Oncogenesis · 2024Article
- Yohimbine Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation and Migration via FOXO3a Factor.International journal of molecular sciences · 2024Article
- An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis.Frontiers in cell and developmental biology · 2024Review
- Increased Oxidative Stress and Decreased Sirtuin-3 and FOXO3 Expression Following Carotid Artery Intimal Injury in Hyperlipidemic Yucatan Microswine.Cardiology and cardiovascular medicine · 2024Article
- Sterol carrier protein 2: A promising target in the pathogenesis of atherosclerosis.Genes & diseases · 2023Review
- FoxO3 and oxidative stress: a multifaceted role in cellular adaptation.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Transcription factors: key regulatory targets of vascular smooth muscle cell in atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2023Review
- FoxO3 normalizes Smad3-induced arterial smooth muscle cell growth.Frontiers in physiology · 2023Article
- The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance.International journal of molecular sciences · 2022Article
- Regulation and Function of Matrix Metalloproteinase-13 in Cancer Progression and Metastasis.Cancers · 2022Review
- STAT3 induces breast cancer growth via ANGPTL4, MMP13 and STC1 secretion by cancer associated fibroblasts.Oncogene · 2022Article
- Effect of tocotrienol on the primary progression of nonalcoholic steatohepatitis in a mouse model.Journal of clinical biochemistry and nutrition · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveVascular smooth muscle cell (VSMC) apoptosis accelerates atherosclerosis and promotes breakdown of the extracellular matrix, but the mechanistic links between these 2 processes are unknown. The forkhead protein FOXO3a (forkhead transcription factor O subfamily member 3a) is activated in human atherosclerosis and induces a range of proapoptotic and other transcriptional targets. We, therefore, determined the mechanisms and consequences of FOXO3a activation in atherosclerosis and arterial remodeling after injury. APPROACH AND
resultsExpression of a conditional FOXO3a allele (FOXO3aA3ER) potently induced VSMC apoptosis, expression and activation of MMP13 (matrix metalloproteinase 13), and downregulation of endogenous TIMPs (tissue inhibitors of MMPs).
conclusionsFOXO3a activation induces VSMC apoptosis and extracellular matrix breakdown, in part, because of transcriptional activation of MMP13. FOXO3a activation promotes atherosclerosis and medial degeneration and increases neointima after injury that is partly dependent on MMP13. FOXO3a-induced MMP activation represents a direct mechanistic link between VSMC apoptosis and matrix breakdown in vascular disease.
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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.