Abstract 340: The Expression and Function of Apol6 in Atherosclerotic Plaques of Apoe-/- Mouse Aorta Tissue
Background: We recently demonstrated that apolipoprotein L6 (ApoL6) regulates apoptosis and autophagy in atherosclerotic lesions, implying that ApoL6 is an important factor that causes plaque instability and a potential therapeutic target for treating atherosclerosis. To further investigate the role of ApoL6 in atherogenesis in vivo, the expression of ApoL6 was knocked down by the liposome-siRNA strategy in the aorta tissue of ApoE-/- mouse.
Methods: Liposomal siRNAs were prepared by using the thin-film hydration method and were labeled with quantum dots (QD). ApoE-/- mice were intravenously injected twice in 1 week with either liposomal control siRNA-QD or liposomal ApoL6 siRNA-QD. We harvested aortic tissue from mice and used immunofluorescence staining to analyze the expression of ApoL6 in atherosclerotic plaque.
Results: Immunofluorescence analysis showed that expression of ApoL6 was elevated in the atherosclerotic plaque and partially co-localized with a macrophage marker CD68 in ApoE-/- mouse. The results suggest a link between ApoL6 and macrophages in the pathobiology of atherosclerotic lesions (Fig. A and B). Confocal microscopy images showed that liposomal ApoL6 siRNA significantly reduced ApoL6 expression (green punctures) in atherosclerotic plaques as compared with liposomal control siRNA (Fig. C).
Conclusion: We established a silencing model of ApoL6 in cardiovascular system of ApoE-/- mouse using liposome-mediated siRNA delivery system. The intravenous injection of liposomal ApoL6 siRNA silences ApoL6 expression in the aortas of ApoE-/- mice and may protect against the development of atherosclerosis.
Author Disclosures: S. Zhaorigetu: None. C. Hu: None. W. Laskey: None. B. Walton: None.
- © 2015 by American Heart Association, Inc.