Extended Data Fig. 6: nt-LNA treatment reduces atherosclerosis without altering lipid or lipoprotein metabolism in Apoe^-/- mice.

a) Female and male Apoe^-/- mice fed a western diet were administered saline (Ctr; n = 4 mice per sex), nt-LNA-A (20 mg/kg; n = 4 mice per sex) or nt-LNA-B (20 mg/kg; n = 4 mice per sex) by intraperitoneal injection once weekly for four weeks. Treatments for each were randomized between cohabitating animals separated by sex. At sacrifice, the aortic sinus was serially sectioned and stained with Oil-Red O to identify atherosclerotic lesions. Scale bar = 500 μm. b) Quantification of lesion area in serial sections and c) sex-normalized, relative lesion area under the curve (n = 8 mice per treatment). d) Plasma of female Apoe^-/- mice treated for 4 weeks with saline (Ctr; n = 10) or nt-LNA (n = 10) were fractionated by size-exclusion chromatography and assessed for total cholesterol (TC) e) Plasma protein levels were assessed by immunoblot of individual cages receiving either Saline/Ctr (n = 5 mice) or nt-LNA (n = 5 mice) treatments (representative images of two independent assessments). f) Quantification of independent immunoblots by densitometry (n = 10 mice per treatment) normalized to C3. g) Lesion area (Oil-red O) of matched sections of the aortic root following treatment with saline (Ctr) or nt-LNA for 4 weeks (n = 10 mice per treatment). h) Hepatic mRNA expression determined by qPCR (n = 10 mice per treatment). Data are mean ± SEM. (c) One-way ANOVA, Sidak’s multiple comparison test, *p < 0.05. **p < 0.01. (f-h) Two-way ANOVA with Benjamini, Krieger and Yekutieli FDR (Q = 0.05), *q < 0.05, **q < 0.01,***q < 0.001. Numerical source data, statistics, exact p values and q values are provided.

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