PT - JOURNAL ARTICLE AU - Katharina Schäfer AU - Khodr Tello AU - Oleg Pak AU - Manuel Richter AU - Mareike Gierhardt AU - Grazyna Kwapiszewska AU - Christine Veith AU - Ludger Fink AU - Henning Gall AU - Matthias Hecker AU - Baktybek Kojonazarov AU - Simone Kraut AU - Kevin Lo AU - Jochen Wilhelm AU - Friedrich Grimminger AU - Werner Seeger AU - Ralph T. Schermuly AU - Hossein A. Ghofrani AU - Daniel Zahner AU - Rüdiger Gerstberger AU - Norbert Weissmann AU - Akylbek Sydykov AU - Natascha Sommer TI - Decreased plasma levels of the brain-derived neurotrophic factor correlate with right heart congestion in pulmonary arterial hypertension AID - 10.1183/23120541.00230-2022 DP - 2023 Jan 01 TA - ERJ Open Research PG - 00230-2022 4099 - http://openres.ersjournals.com/content/early/2022/09/22/23120541.00230-2022.short 4100 - http://openres.ersjournals.com/content/early/2022/09/22/23120541.00230-2022.full AB - Background The brain-derived neurotrophic factor (BDNF) may promote development of pulmonary hypertension (PH) and right ventricular (RV) failure. However, BDNF plasma levels were decreased in patients with left ventricular failure. Therefore, we investigated BDNF plasma levels in PH patients and the role of BDNF in mouse models of PH and isolated RV failure.Methods BDNF plasma levels were correlated to PH in two patient cohorts, including either post- and precapillary PH patients (first cohort) or only precapillary PH patients (second cohort). In the second cohort, RV dimensions and load-independent function were determined by imaging and pressure-volume catheter measurements, respectively. For induction of isolated RV pressure overload, heterozygous Bdnf knockout mice (Bdnf+/−) were subjected to pulmonary arterial banding (PAB). For induction of PH, mice with inducible knockout of BDNF in smooth muscle cells (Bdnf/Smmhc knockout), were exposed to chronic hypoxia.Results Plasma BDNF levels were decreased in patients with PH. After adjustment for co-variables BDNF levels negatively correlated in both cohorts with central venous pressure. In the second cohort, BDNF levels additionally negatively correlated with RV dilatation In animal models, BDNF downregulation attenuated RV dilatation in Bdnf+/− mice after PAB or hypoxic Bdnf/Smmhc knockout mice, although they developed PH to a similar extent.Conclusions Similar to LV failure, circulating levels of BDNF were decreased in PH patients and low BDNF levels were associated with right heart congestion. Decreased BDNF levelsdid not worsen RV dilatation in animal models and thus may be the consequence but not cause of RV dilatation.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.