Brain-derived neurotrophic factor is related with adverse cardiac remodeling and high NTproBNP

Martin Bahls,Marcello R P Markus,Deborah Janowitz,Nele Friedrich,Henry Völzke,Stephanie Könemann,Kristin Wenzel,Marcus Dörr,Stephan B Felix,Matthias Nauck,Hans-Jörgen Grabe,Antje Steveling

doi:10.1038/s41598-019-51776-8

Abstract

The brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for normal cardiac contraction and relaxation. Alterations in BDNF signaling are related to the development of cardiovascular disease. Whether BDNF is related to subclinical cardiac remodeling is unclear. We related BDNF with echocardiographic parameters and NTproBNP in a large population-based cohort (n = 2,976, median age 48 years; 45% male). Transthoracic echocardiography was performed on all subjects and BDNF was measured by ELISA. Study participants with severe kidney dysfunction, previous myocardial infarction, and LV ejection fraction <40% were excluded. Linear regression models were adjusted for age, sex, lean mass, fat mass, current smoking, systolic blood pressure and depression. Low BDNF was associated with high NTproBNP. A 10,000 pg/ml lower BDNF was related with a 2.5 g higher (95%-confidence interval [CI]: 0.2 to 4.9; p = 0.036) LV mass, 0.01 cm posterior wall thickness (0.003 to 0.022; p = 0.007) and 0.02 E/A ratio (0.003 to 0.042, p = 0.026). Here we show that low BDNF levels are related with adverse cardiac remodeling and higher levels of NTproBNP. Further research is warranted to assess if BDNF may be used to monitor neuronal-cardiac damage during CVD progression.

Highlights

The brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for normal cardiac contraction and relaxation
Using data from a large population based study we demonstrate that low BDNF is related with higher levels of the heart failure biomarker NTproBNP and with adverse left ventricular cardiac remodeling
Our results extend the current knowledge by providing evidence for a putative role of BDNF not just in heart failure and during subclinical cardiac dysfunction and remodeling prior to manifest cardiac disease

Summary

Introduction

The brain-derived neurotrophic factor (BDNF) is a neuronal growth factor essential for normal cardiac contraction and relaxation. We show that low BDNF levels are related with adverse cardiac remodeling and higher levels of NTproBNP. Constitutive BDNF signaling is required for physiological murine cardiac contraction and relaxation[4]. BDNF plays a role in the progression of human cardiovascular disease. This neurotrophin promotes atherogenesis and plaque instability via the activation of NAD(P)H oxidase[5]. Previous research suggests a link between BDNF, cardiac function and cardiovascular disease. We tried to improve our understanding of this relationship by assessing the role of BDNF on left ventricular cardiac remodeling and function using data from a population based cohort from northeast Germany. We further explored the association between BDNF and the established heart failure marker N-terminal pro b-type natriuretic peptide (NTproBNP)

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Results

Conclusion