Fig. 2.

Hepatic PCSK9 silencing, hepatic TGs, and LDLR levels in rats. (A) LNP-PCS-A2 mediated dose-dependent lowering of hepatic PCKS9 mRNA and total serum cholesterol 3 days after dose (n = 6 per group). Each value is the group mean ± STDEV. One-way ANOVA with Student's t test. Asterisks represent statistical difference between PBS- and PCSK9 siRNA-treated groups *, P ≤ 0.05; **, P ≤ 0.01. (B) Total serum cholesterol lowering of LNP-PCS-A2 treated rats (n = 6 per group) is maximal (≈60%) by 2 days after dose and returns to baseline over ≈21 days. PCSK9-treated groups are statistically significant (until approximately day 16) compared with PBS and LNP-Crtl groups (one-way ANOVA, Student's t test, with P values of ≤ 0.05). (C) Liver TGs and cholesterol contents from treated and control animals (same as in A). There were no significant differences in the liver TGs (ANOVA: P = 0.824 for cholesterol content ANOVA on ranks; P = 0.935 for LNP-PCS-A2-treated animals vs. the LNP-Crtl- or PBS-treated control groups for TG levels). (D) Immunoblot of liver extracts from LNP-PCS-A2-, LNP-Crtl-, and PBS-treated rats (same as in A). Transferrin receptor (TFR) levels were used to normalize for protein loading. (Note that treated animal lane 15 was a noticeable outlier that did not up-regulate LDLR and on close examination also did not lower PCSK9 levels, possibly because of a misinjection). †, relative to PBS.