ArticlePloS one2016
Development of Accelerated Coronary Atherosclerosis Model Using Low Density Lipoprotein Receptor Knock-Out Swine with Balloon Injury.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021Pooled it
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- Cardiac rehabilitation in porcine models: Advances in therapeutic strategies for ischemic heart disease.Zoological research · 2025Review
- Integrating Computational and Biological Hemodynamic Approaches to Improve Modeling of Atherosclerotic Arteries.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine.Cardiology and cardiovascular medicine · 2023Article
- Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery.Clinical science (London, England : 1979) · 2022Article
- Survival intravascular photoacoustic imaging of lipid-rich plaque in cholesterol fed rabbits.Translational biophotonics · 2022Article
- Article
- Modelling of atherosclerosis in genetically modified animals.American journal of translational research · 2019Review
- An update on the tools for creating transgenic animal models of human diseases - focus on atherosclerosis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2019Review
- A novel swine model for evaluation of dyslipidemia and atherosclerosis induced by human CETP overexpression.Lipids in health and disease · 2017Article
- CRISPR/Cas9-mediated ApoE-/- and LDLR-/- double gene knockout in pigs elevates serum LDL-C and TC levels.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral animal models have facilitated the evaluation and pathological understanding of atherosclerosis, but a definitive animal model of coronary atherosclerosis is not available. We therefore developed low density lipoprotein receptor knockout (LDLR-KO) pigs with hypercholesterolemia, a model which rapidly developed coronary atherosclerosis following balloon injury. METHODS AND
resultsWe deleted LDLR exon regions from cultured porcine fetal fibroblasts and cloned LDLR knockout (LDLR-KO) embryos microinjecting fetal fibroblast nuclei into enucleated oocytes. Twelve LDLR-KO pigs were fed a 2.0% cholesterol and 20% fat diet. Baseline serum LDL cholesterol level was 510.0±86.1 mg/dL. Balloon injury was created in 46 coronary segments and necropsy were obtained 2, 4, 8 and 12 weeks later. Coronary artery sections were reviewed to evaluate lesion progression. We found lipid accumulation with foam cells and inflammatory cells beginning four weeks after balloon injury. The mean ratio of macrophages to plaque area was significantly higher in the four- weeks and eight-week animals compared with those at 2-weeks (8.79% ± 5.98% and 17.00% ± 10.38% vs. 1.14% ± 1.88%, P < 0.0001). At 12 weeks the ratio decreased toward the level at 2 week level (4.00% ± 4.56%, P = 0.66 vs. baseline). Advanced coronary atherosclerotic lesions contained lipid pools at eight-weeks with fibrous components beginning at 12 weeks.
conclusionsWe developed a model of rapid coronary atherosclerosis using LDLR KO pigs with balloon injury. This model may be useful for preclinical evaluation of medication or devices, and may also help investigate mechanisms of plaque progression.
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Registered trials
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