Identification of DKK-1 as a novel mediator of statin effects in human endothelial cells

Non solo un bersaglio delle statine, ma anche un potenziale mediatore dell'organizzazione della matrice extracellulare e dell'attivazione piastrinica. (Sci Rep 2018 Nov 12;8(1):16671)

21 Novembre Nov 2018 22 days ago
  • Pontremoli M, Brioschi M, Baetta R, Ghilardi S, Banfi C

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.

The Authors found that atorvastatin downregulates DKK-1 protein and mRNA expression through the inhibition of Cdc42, Rho and Rac geranylgeranylated proteins. DKK-1 is responsible for the regulation of the 21% of the statin-modulated proteins, which include, among others, clusterin/apoJ, plasminogen activator inhibitor type 1 (PAI-1), myristoylated alanine-rich C-kinase substrate (MARCKS), and pentraxin 3 (PTX3).

DKK-1 is also a potential mediator of the extracellular matrix organization, platelet activation and response to wounding processes induced by statin. DKK-1 is not only a target of statin but it directly regulates the expression of molecules involved in a plethora of biological functions, thus expanding its role, which has been so far restricted mainly to cancer.


Reference
1. Pontremoli M, Brioschi M, Baetta R, Ghilardi S, Banfi C. Identification of DKK-1 as a novel mediator of statin effects in human endothelial cells. Sci Rep 2018 Nov 12;8(1):16671. doi: 10.1038/s41598-018-35119-7. Go to PubMed