title: Levels of DKK1 in patients with acute myocardial infarction and response to atorvastatin.
abstract: The Wnt-LPR5 signalling pathway plays an important role in skeletal homeostasis, especially in regulating osteoblastic activity. Activation of this pathway is regulated by various inhibitors, including DKK1. The objective of this study was to evaluate DKK1 levels in patients with ischemic heart disease, the response to atorvastatin and the relationship with bone mass. Twenty-one patients with acute myocardial infarction and twenty-three controls with a mean age of 61 ± 9 years with acute coronary syndrome were included. Patients were allocated to low (10-20mg) and high doses (40-80 mg) of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk. Patients were studied at hospital admission (baseline) and at 12 months of follow up. DKK1 was determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine (L2-L4) and the femoral neck and trochanter using an X-ray densitometer. Patients had higher levels of DKK1 than controls, (111 ± 41 nmol/l versus 84 ± 27 nmol/l, p=0.014). Osteoporotic patients had higher levels of DKK1 (137.5 ± 33 nmol/l versus 95.4 ± 36 nmol/l, p=0.021). Analysis of the response to atorvastatin showed reduced DKK1 levels. In conclusion, in patients with acute coronary syndrome, atorvastatin decreases DKK1 levels. This may be a previously unreported mechanism of action of atorvastatin on bone, stimulating the Wnt signalling pathway and increasing bone mass.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pérez Castrillón
authors.forename: Angel
authors.initials: A
authors.lastname: San Miguel
authors.forename: Gemma
authors.initials: G
authors.lastname: Vega
authors.forename: Laura
authors.initials: L
authors.lastname: Abad
authors.forename: María
authors.initials: M
authors.lastname: Andres Domingo
authors.forename: Manuel
authors.initials: M
authors.lastname: Gonzalez Sagredo
authors.forename: Daniel
authors.initials: D
authors.lastname: de Luis
authors.forename: Antonio
authors.initials: A
authors.lastname: Duenas-Laita
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C501126:DKK1 protein, human; D006538:Heptanoic Acids; D036341:Intercellular Signaling Peptides and Proteins; D011758:Pyrroles; D000069059:Atorvastatin