ArticleAngiogenesis2021
Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization.
Article in Angiogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- The Compatibility of Astragali Radix and Angelicae Sinensis Radix Attenuates Atherosclerosis by Suppressing Vascular Endothelial PANoptosis via the p38 MAPK/p53 Pathway: A Multi-Omics and Experimental Study.International journal of molecular sciences · 2026Article
- Exploring the potential role of miR-124 in angiogenesis in colorectal cancer.Journal of cancer research and clinical oncology · 2026Article
- Development and validation of a risk prediction model for myocardial hypoperfusion after primary PCI in ST-segment elevation myocardial infarction.Frontiers in cardiovascular medicine · 2026Article
- Modeling hepatocellular carcinoma and its microenvironment on a chip.Cell death discovery · 2025Article
- CDH1 reduces endothelial cell permeability by enhancing CDH5 membrane expression under chronic intermittent hypoxia.European journal of medical research · 2025Article
- Passivating rapidly progressing plaque with refractory angina and intraplaque hemorrhage: case series and literature review.BMC cardiovascular disorders · 2025Review
- The role of cell junctions in atherosclerosis: implications for inflammation, endothelial dysfunction, and plaque stability.Journal of physiology and biochemistry · 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
- Isolation and Purification of Murine Lung Endothelial Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Promising Adventitia in Atherosclerosis.Current vascular pharmacology · 2025Review
- Sepsis-Induced Endothelial Barrier Dysfunction: Mechanisms, Pathology, and Therapeutic Advances.Research (Washington, D.C.) · 2025Review
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- Hypoxic Inducible Factor Stabilization in Pericytes beyond Erythropoietin Production: The Good and the Bad.Antioxidants (Basel, Switzerland) · 2024Review
- Pathological angiogenesis: mechanisms and therapeutic strategies.Angiogenesis · 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
- Comparison the therapeutic effects of bone marrow CD144BioImpacts : BI · 2023Article
- Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts.International journal of molecular sciences · 2022Article
- Molecular Mechanisms Underlying Pathological and Therapeutic Roles of Pericytes in Atherosclerosis.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveStatins pleiotropically provide additional benefits in reducing atherosclerosis, but their effects on intraplaque angiogenesis (IPA) and hemorrhage (IPH) remain unclear. Therefore, we discriminated statin's lipid-lowering dependent and independent effects on IPA and IPH. APPROACH AND
resultsApoE3*Leiden mice are statin-responsive due to ApoE and LDLR presence, but also allow to titrate plasma cholesterol levels by diet. Therefore, ApoE3*Leiden mice were fed a high-cholesterol-inducing-diet (HCD) with or without atorvastatin (A) or a moderate-cholesterol-inducing-diet (MCD). Mice underwent vein graft surgery to induce lesions with IPA and IPH. Cholesterol levels were significantly reduced in MCD (56%) and HCD + A (39%) compared to HCD with no significant differences between MCD and HCD + A. Both MCD and HCD + A have a similar reduction in vessel remodeling and inflammation comparing to HCD. IPA was significantly decreased by 30% in HCD + A compared to HCD or MCD. Atorvastatin treatment reduced the presence of immature vessels by 34% vs. HCD and by 25% vs. MCD, resulting in a significant reduction of IPH. Atorvastatin's anti-angiogenic capacity was further illustrated by a dose-dependent reduction of ECs proliferation and migration. Cultured mouse aortic-segments lost sprouting capacity upon atorvastatin treatment and became 30% richer in VE-Cadherin expression and pericyte coverage. Moreover, Atorvastatin inhibited ANGPT2 release and decreased VE-Cadherin(Y685)-phosphorylation in ECs.
conclusionsAtorvastatin has beneficial effects on vessel remodeling due to its lipid-lowering capacity. Atorvastatin has strong pleiotropic effects on IPA by decreasing the number of neovessels and on IPH by increasing vessel maturation. Atorvastatin improves vessel maturation by inhibiting ANGPT2 release and phospho(Y658)-mediated VE-Cadherin internalization.
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