| First Author | Goettsch C | Year | 2016 |
| Journal | Atherosclerosis | Volume | 251 |
| Pages | 109-118 | PubMed ID | 27318830 |
| Mgi Jnum | J:278772 | Mgi Id | MGI:6356468 |
| Doi | 10.1016/j.atherosclerosis.2016.06.011 | Citation | Goettsch C, et al. (2016) A single injection of gain-of-function mutant PCSK9 adeno-associated virus vector induces cardiovascular calcification in mice with no genetic modification. Atherosclerosis 251:109-118 |
| abstractText | BACKGROUND AND AIMS: Studying atherosclerotic calcification in vivo requires mouse models with genetic modifications. Previous studies showed that injection of recombinant adeno-associated virus vector (AAV) encoding a gain-of-function mutant PCSK9 into mice promotes atherosclerosis. We aimed to study cardiovascular calcification induced by PCSK9 AAV in C57BL/6J mice. METHODS: 10 week-old C57BL/6J mice received a single injection of AAV encoding mutant mPCSK9 (rAAV8/D377Y-mPCSK9). Ldlr(-/-) mice served as positive controls. Mice consumed a high-fat, high-cholesterol diet for 15 or 20 weeks. Aortic calcification was assessed by fluorescence reflectance imaging (FRI) of a near-infrared calcium tracer. RESULTS: Serum levels of PCSK9 (0.14 mug/mL to 20 mug/mL, p < 0.01) and total cholesterol (82 mg/dL to 820 mg/dL, p < 0.01) increased within one week after injection and remained elevated for 20 weeks. Atherosclerotic lesion size was similar between PCSK9 AAV and Ldlr(-/-) mice. Aortic calcification was 0.01% +/- 0.01 in PCSK9 AAV mice and 15.3% +/- 6.1 in Ldlr(-/-) mice at 15 weeks (p < 0.01); by 20 weeks, the PCSK9 AAV mice aortic calcification grew to 12.4% +/- 4.9. Tissue non-specific alkaline phosphatase activity was similar in PCSK9 AAV mice and Ldlr(-/-) mice at 15 and 20 weeks, respectively. As example of the utility of this model in testing modulators of calcification in vivo, PCSK9 AAV injection to sortilin-deficient mice demonstrated reduced aortic calcification by 46.3% (p < 0.05) compared to littermate controls. CONCLUSIONS: A single injection of gain-of-function PCSK9 AAV into C57BL/6J mice is a useful tool to study cardiovascular calcification in mice with no genetic manipulation. |
