biostudies-literaturePontremoli MMinistry of Health, Italy | Agenzia Italiana del Farmaco, Ministero della SaluteMinistry of Health, Italy | Agenzia Italiana del Farmaco, Ministero della Salute (Italian Medicines Agency)16671https://www.ebi.ac.uk/biostudies/studies/S-EPMC6232108biostudies-literatureUnknown8(1)This study shows that DKK-1, a member of the Dickkopf family and a regulator of the Wnt pathways, represents a novel target of statins which, through the inhibition of HMG-CoA reductase and of non-steroidal isoprenoid intermediates, exert extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. We found that atorvastatin downregulates DKK-1 protein (-88.3 ± 4.1%) and mRNA expression (-90 ± 4.2%) through the inhibition of Cdc42, Rho and Rac geranylgeranylated proteins. Further, a combined approach based on the integration of label-free quantitative mass spectrometry based-proteomics and gene silencing allowed us to demonstrate that DKK-1 itself mediates, at least in part, statin effects on human endothelial cells. Indeed, DKK-1 is responsible for the rScientific reportsIdentification of DKK-1 as a novel mediator of statin effects in human endothelial cells.PMC62321082101581Baetta RBanfi CPontremoli MBrioschi MGhilardi SfalseIdentification of DKK-1 as a novel mediator of statin effects in human endothelial cells.This study shows that DKK-1, a member of the Dickkopf family and a regulator of the Wnt pathways, represents a novel target of statins which, through the inhibition of HMG-CoA reductase and of non-steroidal isoprenoid intermediates, exert extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. We found that atorvastatin downregulates DKK-1 protein (-88.3 ± 4.1%) and mRNA expression (-90 ± 4.2%) through the inhibition of Cdc42, Rho and Rac geranylgeranylated proteins. Further, a combined approach based on the integration of label-free quantitative mass spectrometry based-proteomics and gene silencing allowed us to demonstrate that DKK-1 itself mediates, at least in part, statin effects on human endothelial cells. Indeed, DKK-1 is responsible for the r2018-01-01T00:00:00Z2018 Nov2026-05-06T01:03:16.811Z2019-03-27T00:10:15ZS-EPMC62321083042071010.1038/s41598-018-35119-7