Wnt11 preserves mitochondrial membrane potential and protects cardiomyocytes against hypoxia through paracrine signaling

We investigated the effect of Wnt11 on mitochondrial membrane integrity in cardiomyocytes (CMs) and the underlying mechanism of Wnt11‐mediated CM protection against hypoxic injury. A rat mesenchymal stem cell (MSC) line that overexpresses Wnt11 (MSCWnt11) and a control cell line transduced with empt...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2020-02, Vol.121 (2), p.1144-1155
Main Authors: Li, Hong‐Xia, Lin, Jia, Jiang, Bin, Yang, Xiang‐Jun
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Antibodies
Apoptosis
Biotechnology
Cardiomyocytes
cardioprotection
Fibroblast growth factor 2
Fluorescence
Growth factors
Hypoxia
Hypoxia - complications
IGF‐1
Insulin
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor I - metabolism
Insulin-like growth factors
Integrity
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Membrane potential
Membrane Potential, Mitochondrial
Membranes
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Mesenchyme
Mitochondria
mitochondrial membrane integrity
Myocardial Reperfusion Injury - etiology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - pathology
Myocardial Reperfusion Injury - therapy
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Necrosis
Neonates
Paracrine Communication
Paracrine signalling
Rats
Rats, Sprague-Dawley
Signaling
Stem cells
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
VEGF
Wnt Proteins - genetics
Wnt Proteins - metabolism
Wnt11
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Summary:We investigated the effect of Wnt11 on mitochondrial membrane integrity in cardiomyocytes (CMs) and the underlying mechanism of Wnt11‐mediated CM protection against hypoxic injury. A rat mesenchymal stem cell (MSC) line that overexpresses Wnt11 (MSCWnt11) and a control cell line transduced with empty vector (MSCNull) were established to determine the cardioprotective role of Wnt11 in response to hypoxia. Mitochondrial membrane integrity in MSCWnt11 cells was assessed using fluorescence assays. The role of paracrine signaling mediated by vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b‐FGF), and insulin‐like growth factor 1 (IGF‐1) in protecting CMs against hypoxia were investigated using cocultures of primary CMs from neonatal rats with conditioned medium (CdM) from MSCWnt11. MSCWnt11 cells exposed to hypoxia reduced lactate dehydrogenase release from CMs and increased CM survival under hypoxia. In addition, CMs cocultured with CdM that were exposed to hypoxia showed reduced CM apoptosis and necrosis. There was significantly higher VEGF and IGF‐1 release in the MSCWnt11 group compared with the MSCNull group, and the addition of anti‐VEGF and anti‐IGF‐1 antibodies inhibited secretion. Moreover, mitochondrial membrane integrity was maintained in the MSCWnt11 cell line. In conclusion, overexpression of Wnt11 in MSCs promotes IGF‐1 and VEGF release, thereby protecting CMs against hypoxia. Although Wnt11 is known to protect cardiomyocytes (CMs) against hypoxia, its effect on mitochondrial membrane integrity and mechanism of cardioprotection are unclear. By genetically engineering mesenchymal stem cells to overexpress Wnt11, we showed that mitochondrial membrane integrity was maintained in CMs with upregulated Wnt11. In addition, our study revealed that CM protection against hypoxic stress is mediated through the paracrine factors IGF‐1 and vascular endothelial growth factor.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.29349