A Translational Model for Diet-related Atherosclerosis
| Autor: | Christopher S. Rogers, Steven Denham, Thomas Vihtelic, John R. Swart, Chidozie Amuzie, Dale E. Mais |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Statin Normal diet Swine medicine.drug_class Atorvastatin Hypercholesterolemia 030204 cardiovascular system & hematology Diet High-Fat Toxicology Pathology and Forensic Medicine Animals Genetically Modified Translational Research Biomedical 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein Internal medicine medicine Animals Oil Red O Molecular Biology Aorta Cholesterol business.industry Cell Biology Atherosclerosis Femoral Artery Disease Models Animal 030104 developmental biology Endocrinology Receptors LDL chemistry LDL receptor Swine Miniature lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors business Lipoprotein medicine.drug |
| Zdroj: | Toxicologic Pathology. 44:442-449 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623315622304 |
| Popis: | Models of atherosclerosis are used in preclinical studies but often fail to translate to humans. A model that better reflects human atherosclerosis is necessary. We recently engineered the ExeGen™ low-density lipoprotein receptor (LDLR) miniswine, in which the LDL receptor gene is modified to drive hypercholesterolemia and atherosclerosis, and showed diet-related exacerbation of these phenotypes. Five groups of animals, either wild type (+/+) or heterozygous (+/−), were fed either a normal or high-fat diet for 6 months. One group of heterozygous pigs fed a high-fat diet was also administered atorvastatin at 3 mg/kg/day. Clinical chemistry and anatomic pathology parameters were measured biweekly and at termination. The high-fat diet resulted in increased adiposity and interspersion of adipocytes within the salivary glands. The heterozygous pigs on the high-fat diet gained more weight and had significant increases in total cholesterol, high-density lipoprotein, and LDL compared to wild-type animals or heterozygous animals fed a normal diet. Atorvastatin attenuated these parameters, indicating the statin had a beneficial effect, even in a high-fat diet scenario. Atorvastatin treatment also reduced the intensity of Oil Red O staining in pigs on high-fat diet. Atorvastatin-related amelioration of several indices of cardiovascular pathophysiology in this model underscores its utility for drug discovery. |
| Databáze: | OpenAIRE |
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