A novel direct inducible nongenetic murine model of diabetes-aggravated atherosclerosis
| Autor: | S Gaul, K Shahzad, R Medert, I Gadi, C Maeder, D Schumacher, A Wirth, S Fatima, J N Boeckel, H Khawaja, M Brune, P P Nawroth, B Isermann, U Laufs, M Freichel |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | European Heart Journal. 43 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Background and aims Atherosclerosis, the main pathology underlying cardiovascular diseases is accelerated in diabetic patients (1,2). Genetic mouse models require breeding efforts which are time-consuming and costly. Our aim was to establish a new nongenetic model of inducible metabolic risk factors that mimics hyperlipidemia, hyperglycemia, or both and allows the detection of phenotypic differences dependent on the metabolic stressor(s) on any genetic background. Methods and results Wild type mice were injected with gain-of-function PCSK9D377Y (proprotein convertase subtilisin/kexin type 9) mutant adeno-associated viral particles (AAV) and streptozotocin (STZ) and fed either a high-fat diet (HFD) or high-cholesterol/high fat-diet (Paigen diet, PD) for 12 and 20 weeks. LDLR KO mice were used as reference control. Combined hyperlipidemic and hyperglycemic mice (HGHCi), but not hyperlipidemia (HCi) alone, displayed characteristic features of aggravated atherosclerosis characterized by larger and less stable plaques (necrotic core area in HGHCi HFD: 24% vs HCi HFD: 13% vs LDLR KO HFD: 18% area, at 20 weeks p Conclusion We established a nongenetic direct inducible mouse model of diabetes-aggravated atherosclerosis allowing comparative analyses of atherosclerosis in diabetic and non-diabetic conditions and its modification by diet, allowing analyses of multiple metabolic hits in mice. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG) |
| Databáze: | OpenAIRE |
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