Myocardial brain-derived neurotrophic factor regulates cardiac bioenergetics through the transcription factor Yin Yang 1
Journal
Cardiovascular research
Journal Volume
119
Journal Issue
2
Date Issued
2023-03-31
Author(s)
Yang, Xue
Zhang, Manling
Xie, Bingxian
Peng, Zishan
Manning, Janet R.
Zimmerman, Raymond
Wang, Qin
Khalifa, Moustafa
Reynolds, Michael
Jin, Jenny
Om, Matthew
Zhu, Guangshuo
Bedja, Djahida
Jiang, Hong
Jurczak, Michael
Shiva, Sruti
Scott, Iain
O'Rourke, Brian
Kass, David A.
Paolocci, Nazareno
Feng, Ning
Abstract
AIMS: Brain-derived neurotrophic factor (BDNF) is markedly decreased in heart failure patients. Both BDNF and its receptor, tropomyosin-related kinase receptor (TrkB), are expressed in cardiomyocytes; however, the role of myocardial BDNF signalling in cardiac pathophysiology is poorly understood. Here, we investigated the role of BDNF/TrkB signalling in cardiac stress response to exercise and pathological stress. METHODS AND RESULTS: We found that myocardial BDNF expression was increased in mice with swimming exercise but decreased in a mouse heart failure model and human failing hearts. Cardiac-specific TrkB knockout (cTrkB KO) mice displayed a blunted adaptive cardiac response to exercise, with attenuated upregulation of transcription factor networks controlling mitochondrial biogenesis/metabolism, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). In response to pathological stress (transaortic constriction, TAC), cTrkB KO mice showed an exacerbated heart failure progression. The downregulation of PGC-1α in cTrkB KO mice exposed to exercise or TAC resulted in decreased cardiac energetics. We further unravelled that BDNF induces PGC-1α upregulation and bioenergetics through a novel signalling pathway, the pleiotropic transcription factor Yin Yang 1. CONCLUSION: Taken together, our findings suggest that myocardial BDNF plays a critical role in regulating cellular energetics in the cardiac stress response.
Subjects
BDNF | cardiac energetics | heart failure | PGC-1α | YY1
SDGs
Publisher
OXFORD UNIV PRESS
Type
journal article