ArticleArteriosclerosis, thrombosis, and vascular biology2012
Thrombospondin-1 regulates blood flow via CD47 receptor-mediated activation of NADPH oxidase 1.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Dietary Polyphenols-Important Non-Nutrients in the Prevention of Chronic Noncommunicable Diseases. A Systematic Review.Nutrients · 2019Pooled it
- Sex Differences and Oxidative Stress in Cardiovascular Disease.Physiology (Bethesda, Md.) · 2026Review
- A Biomimetic Nanoparticle System Intercepts and Degrades Thrombospondin-1 to Restore Vascular Homeostasis After Ischemic Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Thrombospondin 1-CD47 Signalling Modulates Vascular Smooth Muscle Cell Senescence in Chronic Kidney Disease.International journal of molecular sciences · 2026Article
- Targeting the CD47-SIRPα Axis in Atherosclerosis: From Pathogenesis to Therapeutic Implications.Journal of inflammation research · 2026Review
- Protective strategies and therapeutic interventions for ischemia-reperfusion injury: potential applications in normothermic machine perfusion.Annals of medicine and surgery (2012) · 2025Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion.Acta biochimica et biophysica Sinica · 2025Review
- Macrophages in prostate cancer: dual roles in tumor progression and immune evasion.Journal of translational medicine · 2025Review
- Smooth muscle cell-specific CD47 deletion suppresses atherosclerosis.Life sciences · 2025Article
- Cell autonomous functions of CD47 in regulating cellular plasticity and metabolic plasticity.Cell death and differentiation · 2024Review
- Tolerating CD47.Clinical and translational medicine · 2024Review
- The molecular mechanism of thrombospondin family members in cardiovascular diseases.Frontiers in cardiovascular medicine · 2024Review
- Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.Journal of thrombosis and thrombolysis · 2023Review
- Matricellular proteins in atherosclerosis development.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Thrombospondin-1, CD47, and SIRPα display cell-specific molecular signatures in human islets and pancreata.American journal of physiology. Endocrinology and metabolism · 2023Article
- RNAeLife · 2022Article
- Efficient Ex Vivo Screening of Agents Targeting Thrombospondin1-Induced Vascular Dysfunction Using a Digital Multiwire Myograph System.Methods and protocols · 2021Article
- CD47 and thrombospondin-1 regulation of mitochondria, metabolism, and diabetes.American journal of physiology. Cell physiology · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAlthough the matricellular protein thrombospondin-1 (TSP1) is highly expressed in the vessel wall in response to injury, its pathophysiological role in the development of vascular disease is poorly understood. This study was designed to test the hypothesis that TSP1 stimulates reactive oxygen species production in vascular smooth muscle cells and induces vascular dysfunction by promoting oxidative stress. METHODS AND
resultsNanomolar concentrations of TSP1 found in human vascular disease robustly stimulated superoxide (O(2)(•-)) levels in vascular smooth muscle cells at both cellular and tissue level as measured by cytochrome c and electron paramagnetic resonance. A peptide mimicking the C terminus of TSP1 known to specifically bind CD47 recapitulated this response. Transcriptional knockdown of CD47 and a monoclonal inhibitory CD47 antibody abrogated TSP1-triggered O(2)(•-) in vitro and ex vivo. TSP1 treatment of vascular smooth muscle cells activated phospholipase C and protein kinase C, resulting in phosphorylation of the NADPH oxidase organizer subunit p47(phox) and subsequent Nox1 activation, leading to impairment of arterial vasodilatation ex vivo. Further, we observed that blockade of CD47 and NADPH oxidase 1 gene silencing in vivo in rats improves TSP1-induced impairment of tissue blood flow after ischemia reperfusion.
conclusionsOur data suggest a highly regulated process of reactive oxygen species stimulation and blood flow regulation promoted through a direct TSP1/CD47-mediated activation of Nox1. This is the first report, to our knowledge, of a matricellular protein acting as a ligand for NADPH oxidase activation and through specific engagement of integrin-associated protein CD47.
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What OpenQuestion 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 OpenQuestion graph.