Abstract
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.
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- Received September 20, 2022.
- Accepted September 27, 2022.
- Copyright ©The authors 2023
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