Hypoxia inducible factor signaling and experimental persistent pulmonary hypertension of the newborn.
Hypoxia inducible factor signaling and experimental persistent pulmonary hypertension of the newborn.
复制标题
低氧诱导因子信号传导和新生儿的实验持续性肺动脉高压。
DOI：
10.3389/fphar.2015.00047
复制
发表时间：
2015
影响因子：
5.6
通讯作者：
Steinhorn RH
中科院分区：
文献类型：
--
作者：
Wedgwood S;Lakshminrusimha S;Schumacker PT;Steinhorn RH
Background: Mitochondrial reactive oxygen species (ROS) levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity are increased in a lamb model of persistent pulmonary hypertension of the newborn (PPHN). These events can trigger hypoxia inducible factor (HIF) signaling in response to hypoxia, which has been shown to contribute to pulmonary vascular remodeling in rodent models of pulmonary hypertension. However, the role of HIF signaling in chronic intrauterine pulmonary hypertension is not well understood. Aim: To determine if HIF signaling is increased in the lamb model of PPHN, and to identify the underlying mechanisms. Results: PPHN was induced in lambs by antenatal ligation of the ductus arteriosus at 128 days gestation. After 9 days, lungs and pulmonary artery smooth muscle cells (PASMC) were isolated from control and PPHN lambs. HIF-1α expression was increased in PPHN lungs and HIF activity was increased in PPHN PASMC relative to controls. Hypoxia increased HIF activity to a greater degree in PPHN vs. control PASMC. Control PASMC were exposed to cyclic stretch at 1 Hz and 15% elongation for 24 h, as an in vitro model of vascular stress. Stretch increased HIF activity, which was attenuated by inhibition of mitochondrial complex III and NFκB. Conclusion: Increased HIF signaling in PPHN is triggered by stretch, via mechanisms involving mitochondrial ROS and NFκB. Hypoxia substantially amplifies HIF activity in PPHN vascular cells. Targeting these signaling molecules may attenuate and reverse pulmonary vascular remodeling associated with PPHN.
登录
查看更多内容
影响因子：
3.3
作者：
Diebold I;Petry A;Hess J;Görlach A
通讯作者：
Görlach A
影响因子：
4.8
作者：
Jung, Hye Jin;Shim, Joong Sup;Kwon, Ho Jeong
通讯作者：
Kwon, Ho Jeong
影响因子：
8
作者：
Konduri, GG;Solimano, A;Peliowski, A
通讯作者：
Peliowski, A
影响因子：
6.6
作者：
Diebold, Isabel;Petry, Andreas;Goerlach, Agnes
通讯作者：
Goerlach, Agnes
影响因子：
3.6
作者：
Ambalavanan, N;Bulger, A;Chen, YF
通讯作者：
Chen, YF