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Arteriosclerosis Thrombosis and Vascular BiologyMolecular BiologyPeer-reviewed journal article

Renal Angiotensinogen in Nonhuman Primates is Predominantly Liver-Derived

Masayoshi KukidaiD, Lei CaiiD, Dien YeiD, Hisashi SawadaiD, Yuriko KatsumataiD, Michael FrankliniD, Peter I. HeckeriD, Kenneth S. CampbelliD, A.H. Jan DanseriD, Adam E. MullickiD, Alan DaughertyiD, Ryan E. TemeliD, Hong S. LuiD

PDFDOIPreprint

Abstract

AGT (Angiotensinogen) is the unique substrate of the renin-angiotensin system. Liver is the primary source of circulating AGT. The present study determined whether hepatocyte-derived AGT regulates renal AGT accumulation by injecting ASO (antisense oligonucleotides) targeting hepatocyte-derived AGT (GalNAc AGT ASO) into female cynomolgus monkeys. Hepatocyte-specific inhibition of AGT led to profound reductions of plasma AGT concentrations. AGT protein in S1 and S2 of renal proximal tubules was greatly diminished by GalNAc AGT ASO. Given the similarity between nonhuman primates and human, our findings support the notion that renal AGT is predominantly derived from liver, and liver regulates renal angiotensin II production in humans. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/444555v2_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@292f5aorg.highwire.dtl.DTLVardef@1e3e0aborg.highwire.dtl.DTLVardef@1b331e3org.highwire.dtl.DTLVardef@1904dba_HPS_FORMAT_FIGEXP M_FIG C_FIG

Citations
25
FWCI
2.68
Field percentile
top 8%

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