ArticleJournal of internal medicine2019
Blockade of vascular endothelial growth factor receptor 2 inhibits intraplaque haemorrhage by normalization of plaque neovessels.
Article in Journal of internal medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Endoglin/CD105-Based Imaging of Cancer and Cardiovascular Diseases: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Angiogenic Gene Therapy for Lower Extremity Ischemia: Experimental Advances and Clinical Experience.Cells · 2026Review
- [Effect of preoperative lower-limb muscle strength on perioperative blood loss and early outcomes in total knee arthroplasty].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Article
- Increased Vascular Endothelial Growth Factor Receptor 2 Levels Are Associated With a Higher Occurrence of Coronary Artery Disease in Patients With Obstructive Sleep Apnea.Reviews in cardiovascular medicine · 2026Article
- VEGFR1 as a Target for Cardiovascular Gene Therapy.Journal of cardiovascular translational research · 2025Review
- Circadian rhythms of gut microbiota and plaque vulnerability: mechanisms and chrono-microbiota modulation interventions.Gut microbes · 2025Review
- Reimagining Oncologic Drugs in Atherosclerosis: Emerging Mechanisms and Therapeutic Potential.Biomedicines · 2025Review
- Blockade of YAP Mechanoactivation Prevents Neointima Formation and Adverse Remodeling in Arterialized Vein Grafts.Journal of the American Heart Association · 2025Article
- Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis.Mechanobiology in medicine · 2025Review
- Promising Adventitia in Atherosclerosis.Current vascular pharmacology · 2025Review
- The Role of Red Blood Cells in Cholesterol Accumulation and Atherosclerotic Plaque Instability: A Perspective on Atherosclerosis.Current cardiology reviews · 2025Review
- The "angiogenesis-plaque stability paradox" in atherosclerosis pathogenesis.Frontiers in cardiovascular medicine · 2025Review
- The vascular microenvironment and its stem cells regulate vascular homeostasis.Frontiers in cell and developmental biology · 2025Review
- Article
- Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities.Nature metabolism · 2024Review
- Myeloid PHD2 Conditional Knockout Improves Intraplaque Angiogenesis and Vascular Remodeling in a Murine Model of Venous Bypass Grafting.Journal of the American Heart Association · 2024Article
- Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management.International journal of molecular sciences · 2023Review
- Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis.Biomolecules · 2023Article
- Identification of a Novel Angiogenesis Signalling circSCRG1/miR-1268b/NR4A1 Pathway in Atherosclerosis and the Regulatory Effects of TMP-PF In Vitro.Molecules (Basel, Switzerland) · 2023Article
- Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundPlaque angiogenesis is associated with atherosclerotic lesion growth, plaque instability and negative clinical outcome. Plaque angiogenesis is a natural occurring process to fulfil the increasing demand of oxygen and nourishment of the vessel wall. However, inadequate formed, immature plaque neovessels are leaky and cause intraplaque haemorrhage.
objectiveBlockade of VEGFR2 normalizes the unbridled process of plaque neovessel formation and induces maturation of nascent vessels resulting in prevention of intraplaque haemorrhage and influx of inflammatory cells into the plaque and subsequently increases plaque stability. METHODS AND
resultsIn human carotid and vein graft atherosclerotic lesions, leaky plaque neovessels and intraplaque haemorrhage co-localize with VEGF/VEGFR2 and angiopoietins. Using hypercholesterolaemic ApoE3*Leiden mice that received a donor caval vein interposition in the carotid artery, we demonstrate that atherosclerotic vein graft lesions at t28 are associated with hypoxia, Hif1α and Sdf1 up-regulation. Local VEGF administration results in increased plaque angiogenesis. VEGFR2 blockade in this model results in a significant 44% decrease in intraplaque haemorrhage and 80% less extravasated erythrocytes compared to controls. VEGFR2 blockade in vivo results in a 32% of reduction in vein graft size and more stable lesions with significantly reduced macrophage content (30%), and increased collagen (54%) and smooth muscle cell content (123%). Significant decreased VEGF, angiopoietin-2 and increased Connexin 40 expression levels demonstrate increased plaque neovessel maturation in the vein grafts. VEGFR2 blockade in an aortic ring assay showed increased pericyte coverage of the capillary sprouts.
conclusionInhibition of intraplaque haemorrhage by controlling neovessels maturation holds promise to improve plaque stability.
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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.