Abstract 14074: Oral ApoA-I Mimetic Tg6F Enhances Ezetimibe Amelioration of Dyslipidemia
Introduction: Recent reports indicate that as a single agent, ezetimibe or an apoA-I mimetic peptide can modulate trans-intestinal cholesterol efflux (TICE).
Hypothesis: We hypothesized that if ezetimibe and an apoA-I mimetic peptide were acting on the same target, and if the two agents were given together at near maximal doses of each, the resulting readouts would be significantly less than additive.
Methods: Female LDLR null mice (n = 20 per group) were fed a chow or Western diet (WD) without or with Ezetimibe (EZE) at 10 mg/kg/day or with a concentrate of transgenic tomatoes at 0.06% by weight expressing a control marker protein (EV) or the apoA-I mimetic peptide 6F (Tg6F), or the mice were fed WD + EZE + EV or WD + EZE + Tg6F added together at the same doses as for the single agents. After 2 weeks levels of plasma total cholesterol, triglycerides, HDL-cholesterol and paraoxonase-1 (PON) activity were determined.
Results: Plasma total cholesterol levels (mg/dL) on chow were 53.4 ± 19; on WD the levels were 635 ± 79; on WD + EV the levels were 606 ± 107; on WD + EZE the levels were 535 ± 82; on WD + EZE + EV the levels were 543 ± 125; on WD + Tg6F the levels were 502 ± 113; on WD + EZE + Tg6F the levels were 285 ± 36. The addition of EV did not significantly change results; WD + EZE and WD + Tg6F were significantly different from WD alone (p <0.0005), but were not significantly different from each other. WD + EZE + Tg6F was significantly different from all other groups (p <0.0001). Similar results were found for the other parameters measured.
Conclusions: The apoA-I mimetic Tg6F significantly enhanced ezetimibe amelioration of dyslipidemia in this mouse model.
Author Disclosures: P. Mukherjee: None. G. Hough: None. A. Chattopadhyay: None. S.T. Reddy: Employment; Significant; UCLA. Research Grant; Significant; HL30568. Ownership Interest; Significant; Bruin Parma. M. Navab: Employment; Significant; UCLA. Research Grant; Significant; HL30568. Ownership Interest; Significant; Bruin Pharma. A.M. Fogelman: Employment; Significant; UCLA. Research Grant; Significant; HL30568. Ownership Interest; Significant; Bruin Pharma. Other; Significant; Officer in Bruin Pharma.
- © 2016 by American Heart Association, Inc.