Targeting ApoC3 Paradoxically Aggravates Atherosclerosis in Hamsters With Severe Refractory Hypercholesterolemia

Figures

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  Figure 1. Effects of ApoC3 deficiency on lipid metabolism in LDLR−/− hamsters. (A) Generation of DKO hamster model. (B) Hepatic Apoc3 mRNA expression levels were determined in indicated animals on chow at 12 weeks old. (C) Timeline of the whole experiments in this study. High-cholesterol/high-fat diet (HCHF) contains 0.5% cholesterol and 20% fat. (D) Measurement of body weight during the 16-week experiment. (E) Fasting plasma TG and TC levels in the indicated animal on chow or HCHF diet. (F) The distribution of TG and cholesterol in pooled plasma samples from the indicated animals after 12-week HCHF diet feeding and representative western blots of ApoB, ApoE, and ApoA1 in eluted fractions. n = 4–5/group. Data are expressed as mean ± SEM, analyzed by two-way ANOVA or Student's t-test after D'Agostino–Pearson's normality test using Prism 8.0.

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  Figure 2. Morphological analysis of atherosclerosis and fatty liver in LDLR−/− and DKO hamsters on HCHF diet. (A) Representative en-face images of the whole aorta. Arrows indicate positive staining. (B) Quantification of the lesion sizes in the whole aorta. (C) Analysis of the components in atherosclerotic plaques by immunofluorescence in HCHF diet-fed animals. Representative staining of ApoB and CD68 in the atherosclerotic lesions of the aortic root. The areas enclosed by white-dotted lines show the plaques in the aortic root. (D) Representative ORO staining of the aortic root. Black arrows indicate ORO-positive staining. (E) Quantification of the lesion areas in the aortic root. (F) Representative images of ORO-stained cryosections from liver samples. n=4/group. (G) Quantification of the ORO positive areas in the aortic root from (F). (H) Immunofluorescence analysis of macrophage infiltration (CD68) in the liver. n = 4/group. (I) Quantification of the positive sizes in the liver. (J) Fasting plasma ALT and AST levels after 12-week HCHF diet feeding. Data are expressed as mean ± SEM, analyzed by two-way ANOVA or Student's t-test after D'Agostino–Pearson's normality test using Prism 8.0.