ArticleGene therapy2011
Systemic human Netrin-1 gene delivery by adeno-associated virus type 8 alters leukocyte accumulation and atherogenesis in vivo.
Article in Gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Netrin-1 suppresses CCL2-driven macrophage migration: implications for modulating vascular inflammation and aortic sinus enlargement in hyperlipidaemic mice.Journal of molecular and cellular cardiology plus · 2026Article
- Neuroimmune circuits in the plaque and bone marrow regulate atherosclerosis.Cardiovascular research · 2025Review
- Netrin-1 and RGMa: Novel Regulators of Atherosclerosis-Related Diseases.Cardiovascular drugs and therapy · 2025Review
- Netrin-1 and RGMa: Novel Regulators of Atherosclerosis-Related Diseases.Cardiovascular drugs and therapy · 2025Review
- Molecular Mechanisms of Ischemic Stroke: A Review Integrating Clinical Imaging and Therapeutic Perspectives.Biomedicines · 2024Review
- Association between serum netrin-1 levels and early neurological deterioration after acute ischemic stroke.Frontiers in neurology · 2022Article
- Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology.Biomedicines · 2021Article
- Neuronal guidance proteins in cardiovascular inflammation.Basic research in cardiology · 2021Review
- The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process.Cardiovascular therapeutics · 2021Review
- Role of microRNA in CB1 antagonist-mediated regulation of adipose tissue macrophage polarization and chemotaxis during diet-induced obesity.The Journal of biological chemistry · 2019Article
- Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in AβFrontiers in aging neuroscience · 2019Article
- Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications.Journal of diabetes research · 2018Review
- Systemic delivery of adeno-associated viral vectors.Current opinion in virology · 2016Review
- Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement Component C5a.PloS one · 2016Article
- AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet.Journal of translational medicine · 2015Article
- Aspirin-induced histone acetylation in endothelial cells enhances synthesis of the secreted isoform of netrin-1 thus inhibiting monocyte vascular infiltration.British journal of pharmacology · 2015Article
- AAV2/8-hSMAD3 gene delivery attenuates aortic atherogenesis, enhances Th2 response without fibrosis, in LDLR-KO mice on high cholesterol diet.Journal of translational medicine · 2014Article
- Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity.Nature medicine · 2014Article
- Article
- Endothelial expression of guidance cues in vessel wall homeostasis dysregulation under proatherosclerotic conditions.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atherosclerosis is an inflammatory disorder of arteries. Atherosclerotic plaque, in its early to intermediate stages, is composed largely of lipid-engorged foam cells. These foam cells are derived from the trafficking of monocytes (Mo) into the arterial intima, attracted to the site by chemoattractants. Given that foam cells are derived from the trafficking of Mo, the use of Netrin-1, an Mo chemorepellent, may be useful in limiting Mo accumulation and subsequent plaque formation. To investigate the potential of Netrin-1 for limiting atherosclerosis, we systemically delivered its human (h) cDNA by adeno-associated virus type 8 (AAV8, single-stranded structure) delivery into low-density lipoprotein receptor knockout (LDLR-/-) mice and placed the animals on a high cholesterol diet (HCD). Compared with control neomycin resistance (Neo) gene delivery/HCD, hNetrin-1 delivery resulted in a significant reduction in plaque formation, as determined by larger aortic lumen size, thinner intima-media thickness and lower blood velocity than the Neo/HCD control (all statistically significant). Indices of monocyte/macrophage (Mo/MΦ) accumulation, CD68, integrin, alpha M (ITGAM) and egf-like module containing, mucin-like, hormone receptor-like 1 (EMR-1), were reduced in hNetrin-1/HCD-treated animal's aortas and spleens compared with Neo/HCD-treated animals. Unexpectedly, CD25 and foxp3 (regulatory T cells (Tregs)) in the aorta were strongly upregulated. This is the first time the Mo/MΦ chemorepellent approach, and specific Netrin-1 gene delivery, has been performed for the reduction of Mo/MΦ burden and atherosclerosis. In addition, Netrin-1 has never before been linked to altered Treg levels. These data strongly suggest that hNetrin-1 gene delivery can reduce Mo/MΦ accumulation, inflammation and subsequent plaque formation.
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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.