Halmetoja, E., Nagy, I., Szabo, Z., Alakoski, T., Yrjölä, R., Vainio, L., Viitavaara, E., Lin, R., Rahtu‐Korpela, L., Vainio, S., Kerkelä, R., & Magga, J. (2022). Wnt11 in regulation of physiological and pathological cardiac growth. The FASEB Journal, 36(10). https://doi.org/10.1096/fj.202101856RRRR
Wnt11 in regulation of physiological and pathological cardiac growth
|Author:||Halmetoja, Eveliina1; Nagy, Irina2; Szabo, Zoltan1;|
1Research Unit of Biomedicine, University of Oulu, Oulu, Finland
2Department of Clinical Chemistry, Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu and Northern Finland Laboratory Centre NordLab, Oulu University Hospital, Oulu, Finland
3Laboratory of Developmental Biology, Center for Cell Matrix Research, University of Oulu, Oulu, Finland
4Kvantum Institute, Infotech Oulu, University of Oulu, Oulu, Finland
5Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
6Biocenter Oulu, University of Oulu, Oulu, Finland
|Online Access:||PDF Full Text (PDF, 13.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022122173167
John Wiley & Sons,
|Publish Date:|| 2022-12-21
Wnt11 regulates early cardiac development and left ventricular compaction in the heart, but it is not known how Wnt11 regulates postnatal cardiac maturation and response to cardiac stress in the adult heart. We studied cell proliferation/maturation in postnatal and adolescent Wnt11 deficient (Wnt11−/−) heart and subjected adult mice with partial (Wnt11+/−) and complete Wnt11 (Wnt11−/−) deficiency to cardiac pressure overload. In addition, we subjected primary cardiomyocytes to recombinant Wnt proteins to study their effect on cardiomyocyte growth. Wnt11 deficiency did not affect cardiomyocyte proliferation or maturation in the postnatal or adolescent heart. However, Wnt11 deficiency led to enlarged heart phenotype that was not accompanied by significant hypertrophy of individual cardiomyocytes. Analysis of stressed adult hearts from wild-type mice showed a progressive decrease in Wnt11 expression in response to pressure overload. When studied in experimental cardiac pressure overload, Wnt11 deficiency did not exacerbate cardiac hypertrophy or remodeling and cardiac function remained identical between the genotypes. When subjecting cardiomyocytes to hypertrophic stimulus, the presence of recombinant Wnt11 together with Wnt5a reduced protein synthesis. In conclusion, Wnt11 deficiency does not affect postnatal cardiomyocyte proliferation but leads to cardiac growth. Interestingly, Wnt11 deficiency alone does not substantially modulate hypertrophic response to pressure overload in vivo. Wnt11 may require cooperation with other noncanonical Wnt proteins to regulate hypertrophic response under stress.
The FASEB journal
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by research funding from Academy of Finland grants 268505 (J.M.) and 297094 (R.K.); Aarne Koskelo Foundation (E.H.); Paavo Nurmi Foundation (E.H.) and the Finnish Foundation for Cardiovascular Research (Z.S., R.K.).
|Academy of Finland Grant Number:||
268505 (Academy of Finland Funding decision)
297094 (Academy of Finland Funding decision)
© 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.