Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

Autoři	HARTMAN William HELÁN Martin SMELTER Dan SATHISH Venkatashelem THOMPSON Michael PABELICK Chistina M. JOHNSON Bruce PRAKASH Y.S.
Rok publikování	2015
Druh	Článek v odborném periodiku
Časopis / Zdroj	PLOS ONE
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	Odkaz na fulltext článku
Doi	http://dx.doi.org/10.1371/journal.pone.0129489
Obor	Kardiovaskulární nemoci včetně kardiochirurgie
Klíčová slova	BDNF; Hypoxia; Pulmonary Artery
Popis	Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxiaenhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1 inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia- induced pulmonary vascular diseases, and thus a potential target for therapy.