J 2015

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

HARTMAN, William, Martin HELÁN, Dan SMELTER, Venkatashelem SATHISH, Michael THOMPSON et. al.

Základní údaje

Originální název

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

Autoři

HARTMAN, William (840 Spojené státy), Martin HELÁN (203 Česká republika, garant, domácí), Dan SMELTER (840 Spojené státy), Venkatashelem SATHISH (840 Spojené státy), Michael THOMPSON (840 Spojené státy), Chistina M. PABELICK (840 Spojené státy), Bruce JOHNSON (840 Spojené státy) a Y.S. PRAKASH (840 Spojené státy)

Vydání

PLOS ONE, San Francisco, Public Library of Science, 2015, 1932-6203

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.057

Kód RIV

RIV/00216224:14110/15:00083443

Organizační jednotka

Lékařská fakulta

UT WoS

000358546400003

Klíčová slova anglicky

BDNF; Hypoxia; Pulmonary Artery

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 28. 4. 2016 13:42, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

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.