Abstract 12042: A Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac LDLR Expression

• Published in: Circulation (New York, N.Y.) N.Y.), 2022-11, Vol.146 (Suppl_1), p.A12042-A12042
• Main Authors: Williams, Monique M, Condor Capcha, Jose Manuel, Iansen Irion, Camila, Seo, Grace, Lambert, Guerline, Kamiar, Ali, Kanashiro-Takeuchi, Rosemeire M, Takeuchi, Lauro, Saad, Ali, Mendez, Armando J, Webster, Keith A, Goldberger, Jeffrey J, Hare, Joshua M, Shehadeh, Lina A
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.12042

BackgroundHFpEF prevalence has surpassed that of HFrEF. Elevated accumulation of myocardial lipids is a prominent feature of HFpEF patients and the gene for lipoprotein lipase (LPL) in cardiac biopsies is decreased compared with HFrEF or healthy controls. Poloxamer-407 (p407) induces hyperlipidemia by blocking LPL and increasing plasma triglycerides (TG) and LDL cholesterol. We hypothesized that hyperlipidemia driven by p407 and overexpression (OE) of cardiac LDLR in mice mimics a subset of human HFpEF. MethodsWT-129 mice were subject to 4 wks of biweekly i.p. p407-injections with or without a single i.v. injection of AAV9-cTnT-LDLR (n=31); AAV9-cTnT-Luciferase control (n=11), or single i.v. injection with AAV9-cTnT-LDLR alone (n=10). Treatment groups were compared to an untreated group (n=26). Echo, blood pressure (BP), whole-body plethysmography (WBP), ECG telemetry, activity wheel monitoring (AWM), biochemical tests, and histological changes were assessed at 4-8 wks. ResultsAt 4 wks, p407 and LDLR OE led to diastolic dysfunction (DD) (prolonged IVRT, decreased E/A (p