Pyrroloquinoline Quinone inhibits PCSK9, augments LDLR recycling and enhances the effect of atorvastatin

High fat diet intake or statin therapy are known to increase the expression of PCSK9, a key factor involved in the lipid metabolism. Inhibition of PCSK9 is a potential novel strategy for treatment of CVD. Aim of the present study is to investigate the effect of PQQ and atorvastatin on PCSK9 expression in high fat, 10% fructose diet (HFFD) fed rats. Rats received HFFD for 10 weeks followed by treatment of 5 weeks with ATS 10 or 20 mg/kg, PQQ 10 or 20 mg/kg, p.o. per se or in combinations. The effect of the treatments on serum lipid profile, transaminases and PCSK9 concentrations was estimated. Hepatic expressions of PCSK9 and LDLR were quantified by real time quantitative Polymerase chain reaction (RT-qPCR) and western blotting analysis. Compared with the positive control, rats receiving PQQ and ATS showed significant decrease in serum levels of triglycerides, total cholesterol, LDL, VLDL, non-HDL and atherogenic index. Further, drug treatment resulted in decreased serum ALT and AST levels (P < 0.0001). PQQ in combination with atorvastatin reduced serum PCSK9 levels (P < 0.0001) while downregulating the hepatic expression of PCSK9 (P < 0.0001) and increasing the expression of LDL-R (P < 0.001) and rescuing its degradation. PQQ along with atorvastatin prevented the LDLR degradation that was induced in the HFFD fed rats by decreasing PCSK9 expression. The results support an improvement in cholesterol management by adding PQQ to statin treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/485060v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1fe9202org.highwire.dtl.DTLVardef@23f497org.highwire.dtl.DTLVardef@8f15caorg.highwire.dtl.DTLVardef@1df8630_HPS_FORMAT_FIGEXP M_FIG C_FIG