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Global Translational Medicine GalNAc AGT ASO reduce atherosclerosis

A B C

D

Figure 2. Antisense oligonucleotides targeting hepatic angiotensinogen attenuated liver steatosis. (A) Liver weight at termination. (B) Liver total cholesterol
concentration (normalized by liver weight). (C) Liver triglycerides concentration (normalized by liver weight). (D) Hematoxylin and eosin (H and E)
staining (paraffin-embedded sections) and Oil Red O (ORO) staining (fresh-frozen sections) of liver sections; scale bar = 200 µm. N = 6 – 10 per group.
GalNAc AGT ASO: N-acetylgalactosamine-conjugated antisense oligonucleotides targeting angiotensinogen; PBS: Phosphate-buffered saline.

in a dose-independent manner. H&E staining and Oil Red and losartan, we began feeding the Western diet 1 week
O staining revealed diminished neutral lipid accumulation after the initiation of GalNAc AGT ASO (Figure 3B).
in mice administered GalNAc AGT ASO at all doses GalNAc AGT ASO significantly reduced plasma AGT
compared to the vehicle group (Figure 2D). concentrations, while losartan had no effect (Figure 3C).
A similar pattern was observed for hepatic AGT mRNA
3.2. Comparisons between N-acetylgalactosamine- abundance (Figure 3D). As expected, both drugs increased
conjugated antisense oligonucleotides targeting plasma renin concentrations and renal renin mRNA
angiotensinogen and losartan abundance (Figure 4A and B), but the effects of GalNAc

A single dose of GalNAc AGT ASO reduced plasma AGT AGT ASO was greater than that of losartan. This coincided
maximally within 3 days after the injection (Figure 3A). with the effect on systolic BP (Figure 4C), which was
Therefore, when comparing GalNAc AGT ASO (5 mg/kg) lowered more significantly by GalNAc AGT ASO. In

Volume 2 Issue 1 (2023) 5 https://doi.org/10.36922/gtm.288