The cardiokine secreted Frizzled-related protein 3, a modulator of Wnt signalling, in clinical and experimental heart failure
| Autor: | Alexandra Vanessa Finsen, Arnt E. Fiane, Ida G. Lunde, Arne Yndestad, Erik T. Askevold, Mari E. Strand, S. Aakhus, Ole Jørgen Kaasbøll, Geir Christensen, Lars Gullestad, Luigi Tavazzi, Thor Ueland, Leif Erik Vinge, Serge Masson, Geir Florholmen, Stig Haugset Nymo, Roberto Latini, Christen P. Dahl, Ingrid Kristine Ohm, P. Aukrust, Håvard Attramadal |
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| Přispěvatelé: | University of Zurich, Ueland, T, Askevold, Et, Aukrust, P, Nymo, Sh, Lunde, Ig, Kaasbøll, Oj, Aakhus, S, Florholmen, G, Ohm, Ik, Strand, Me, Attramadal, H, Fiane, A, Dahl, Cp, Finsen, Av, Vinge, Le, Christensen, G, Yndestad, A, Gullestad, L, Latini, R, Masson, S, Tavazzi, L, Ueland, T., PERRONE FILARDI, Pasquale |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Left Myocardial Infarction genetics/metabolism Kaplan-Meier Estimate Inbred C57BL Muscle hypertrophy Ventricular Dysfunction Left Mice Ventricular Dysfunction genetics Myocardial infarction Wnt Signaling Pathway Cellular localization Wnt signalling Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA Regulation of gene expression Wnt signaling pathway Middle Aged Disease Progression SFRP3 Female Cardiokine Heart failure Hypertrophy Aged Animals Gene Expression Regulation Humans Mice Inbred C57BL Myocardium Patient Acuity Proportional Hazards Models Disease Models Animal Heart Failure Proteins Internal Medicine Human metabolism/pathology medicine.medical_specialty 610 Medicine & health 11171 Cardiocentro Ticino metabolism/pathology/physiopathology Internal medicine medicine Proportional hazards model business.industry Animal Protein Aged Animals Disease Models Animal Disease Progression Female Gene Expression Regulation Heart Failure etiology/genetics/metabolism/mortality/pathology/physiopathology Humans Kaplan-Meier Estimate Male Mice Mice Inbred C57BL Middle Aged Myocardial Infarction metabolism Myocardium metabolism/pathology Patient Acuity Proportional Hazards Models Proteins genetics/metabolism Ventricular Dysfunction metabolism/pathology/physiopathology Wnt Signaling Pathway medicine.disease etiology/genetics/metabolism/mortality/pathology/physiopathology In vitro Endocrinology 2724 Internal Medicine Disease Models Proportional Hazards Model business metabolism |
| Popis: | Objectives Experimental studies have shown involvement of Wnt signalling in heart failure (HF). We hypothesized that secreted frizzled-related protein 3 (sFRP3), a modulator of Wnt signalling, is related to the progression of HF. Design Circulating sFRP3 was measured in 153 HF patients and compared with 25 healthy controls. The association of sFRP3 with mortality was evaluated in 1202 patients (GISSI-HF trial). sFRP3 mRNA expression was assessed in failing human and murine left ventricles (LV), and cellular localization was determined after fractioning of myocardial tissue. In vitro studies were carried out in cardiac fibroblasts subjected to cyclic mechanical stretch. Results (i) Heart failure patients had significantly raised serum sFRP3 levels compared with controls, (ii) during a median follow-up of 47 months, 315 patients died in the GISSI-HF substudy. In univariable Cox regression, tertiles of baseline sFRP3 concentration were significantly associated with all-cause and cardiovascular mortality. After adjustment for demographic and clinical variables, but not for CRP and NT-proBNP, the associations with mortality remained significant for the third tertile (all-cause, HR 1.45, P = 0.011; cardiovascular, HR 1.66, P = 0.003), (iii) sFRP3 mRNA expression was increased in failing human LV, with a decline following LV assist device therapy. LV from post-MI mice showed an increased sFRP3 mRNA level, particularly in cardiac fibroblasts, and (iv) mechanical stretch enhanced sFRP3 expression and release in myocardial fibroblasts. Conclusion There is an association between increased sFRP3 expression and adverse outcome in HF, suggesting that the failing myocardium itself contributes to an increase in circulating sFRP3. |
| Databáze: | OpenAIRE |
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