TY - JOUR
T1 - The Beneficial Effects of UM206 on Wound Healing After Myocardial Infarction in Mice Are Lost in Follow-Up Experiments
AU - Daskalopoulos, Evangelos P.
AU - Hermans, Kevin C. M.
AU - Debets, Jacques
AU - Strzelecka, Agnieszka
AU - Leenders, Peter
AU - Vervoort-Peters, Lily
AU - Janssen, Ben J. A.
AU - Blankesteijn, W. Matthijs
N1 - Funding Information:
We would like to thank Dr. Peter Timmerman and Dr. Nicolas Dailly, Pepscan Therapeutics B.V., Lelystad, Netherlands for their help in determining the effect of oxidation on the effect of UM206. The technical support of Gregorio Fazzi and Dennis Suylen is gratefully acknowledged. Funding. The studies described in this manuscript were supported by grants from the Dutch Heart Foundation (2010B196) and Cyttron II (FES0908), Dutch Ministry of Economic Affairs.
Funding Information:
The studies described in this manuscript were supported by grants from the Dutch Heart Foundation
Publisher Copyright:
© Copyright © 2019 Daskalopoulos, Hermans, Debets, Strzelecka, Leenders, Vervoort-Peters, Janssen and Blankesteijn.
PY - 2019/9/18
Y1 - 2019/9/18
N2 - Introduction: An inadequate wound healing following myocardial infarction (MI) is one of the main etiologies of heart failure (HF) development. Interventions aiming at improving this process may contribute to preserving cardiac function after MI. Our group, as well as others, have demonstrated the crucial role of Wnt/frizzled signaling in post-MI remodeling. In this overview, we provide the results of different studies aimed at confirming an initial study from our group, in which we observed beneficial effects of administration of a peptide fragment of Wnt5a, UM206, on infarct healing in a mouse MI model.Methods: Mice were subjected to permanent left coronary artery ligation, and treated with saline (control) or UM206, administered via osmotic minipumps. Cardiac function was assessed by echocardiography and hemodynamic measurements, while infarct size and myofibroblast content were characterized by (immuno)histochemistry.Results: In total, we performed seven follow-up studies, but we were unable to reproduce the beneficial effects of UM206 on infarct healing in most of them. Variations in dose and timing of UM206 administration, its manufacturer and the genetic background of the mice could not restore the phenotype. An in-depth analysis of the datasets revealed that the absence of effect of UM206 coincided with a lack of adverse cardiac remodeling and HF development in all experimental groups, irrespective of the treatment.Discussion: Irreproducibility of experimental observations is a major issue in biomedical sciences. It can arise from a relatively low number of experimental observations in the original study, a faulty hypothesis or a variation in the experimental model that cannot be controlled. In this case, the lack of adverse cardiac remodeling and lung weight increases in the follow-up studies point out to altered experimental conditions as the most likely explanation.
AB - Introduction: An inadequate wound healing following myocardial infarction (MI) is one of the main etiologies of heart failure (HF) development. Interventions aiming at improving this process may contribute to preserving cardiac function after MI. Our group, as well as others, have demonstrated the crucial role of Wnt/frizzled signaling in post-MI remodeling. In this overview, we provide the results of different studies aimed at confirming an initial study from our group, in which we observed beneficial effects of administration of a peptide fragment of Wnt5a, UM206, on infarct healing in a mouse MI model.Methods: Mice were subjected to permanent left coronary artery ligation, and treated with saline (control) or UM206, administered via osmotic minipumps. Cardiac function was assessed by echocardiography and hemodynamic measurements, while infarct size and myofibroblast content were characterized by (immuno)histochemistry.Results: In total, we performed seven follow-up studies, but we were unable to reproduce the beneficial effects of UM206 on infarct healing in most of them. Variations in dose and timing of UM206 administration, its manufacturer and the genetic background of the mice could not restore the phenotype. An in-depth analysis of the datasets revealed that the absence of effect of UM206 coincided with a lack of adverse cardiac remodeling and HF development in all experimental groups, irrespective of the treatment.Discussion: Irreproducibility of experimental observations is a major issue in biomedical sciences. It can arise from a relatively low number of experimental observations in the original study, a faulty hypothesis or a variation in the experimental model that cannot be controlled. In this case, the lack of adverse cardiac remodeling and lung weight increases in the follow-up studies point out to altered experimental conditions as the most likely explanation.
KW - myocardial infarction
KW - cardiac remodeling
KW - heart failure
KW - Wnt/frizzled signaling
KW - receptor blockade
KW - peptide fragment
U2 - 10.3389/fcvm.2019.00118
DO - 10.3389/fcvm.2019.00118
M3 - Article
C2 - 31620445
SN - 2297-055X
VL - 6
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 118
ER -