Development of Human‐Like Advanced Coronary Plaques in Low‐Density Lipoprotein Receptor Knockout Pigs and Justification for Statin Treatment Before Formation of Atherosclerotic Plaques
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Le résumé fourni par la source
BACKGROUND: Although clinical trials have proved that statin can be used prophylactically against cardiovascular events, the direct effects of statin on plaque development are not well understood. We generated low-density lipoprotein receptor knockout (LDLR(-/-)) pigs to study the effects of early statin administration on development of atherosclerotic plaques, especially advanced plaques. METHODS AND RESULTS: LDLR(-/-) pigs were generated by targeted deletion of exon 4 of the LDLR gene. Given a standard chow diet, LDLR(-/-) pigs showed atherosclerotic lesions starting at 6 months of age. When 3-month-old LDLR(-/-) pigs were fed a high-cholesterol, high-fat (HCHF) diet for 4 months (HCHF group), human-like advanced coronary plaques developed. We also fed 3-month-old LDLR(-/-) pigs an HCHF diet with pitavastatin for 4 months (Statin Prophylaxis Group). Although serum cholesterol concentrations did not differ significantly between the 2 groups, intravascular ultrasound revealed 52% reduced plaque volume in statin-treated pigs. Pathological examination revealed most lesions (87%) in the statin prophylaxis group were early-stage lesions, versus 45% in the HCHF diet group (P<0.01). Thin-cap fibroatheroma characterized 40% of the plaques in the HCHF diet group versus 8% in the statin prophylaxis group (P<0.01), intraplaque hemorrhage characterized 11% versus 1% (P<0.01), and calcification characterized 22% versus 1% (P<0.01). CONCLUSIONS: Results of our large animal experiment support statin prophylaxis before the occurrence of atherosclerosis. Early statin treatment appears to retard development of coronary artery atherosclerosis and ensure lesion stability. In addition, the LDLR(-/-) pigs we developed represent a large animal model of human-like advanced coronary plaque suitable for translational research.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Development of Human‐Like Advanced Coronary Plaques in Low‐Density Lipoprotein Receptor Knockout Pigs and Justification for Statin Treatment Before Formation of Atherosclerotic Plaques
- Date Crossref
- 03/04/2016
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Nihon University Department of Advanced Cardiovascular Imaging pays non établi dans la noticeUniversité ou école supérieure
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Institute of Agrobiological Sciences pays non établi dans la noticeStructure de recherche
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Tohoku University pays non établi dans la noticeUniversité ou école supérieure
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Suzuki (Japan) pays non établi dans la noticeEntreprise
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Transgenic Pig Research Unit pays non établi dans la noticeStructure de recherche
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Graduate School of Agricultural Science Laboratory of Mucosal Immunology pays non établi dans la noticeUniversité ou école supérieure
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Animal Genome Research Unit pays non établi dans la noticeStructure de recherche
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Prime Tech Ltd pays non établi dans la noticeEntreprise
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College of Bioresource Sciences Department of Animal Science and Resources pays non établi dans la noticeUniversité ou école supérieure
Department of Advanced Cardiovascular Imaging — Nihon University, Institute of Agrobiological Sciences et Tohoku University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.