Impaired cerebral angiogenesis in the fetal lamb model of persistent pulmonary hypertension.
Impaired cerebral angiogenesis in the fetal lamb model of persistent pulmonary hypertension.
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DOI:
10.1016/j.ijdevneu.2014.08.003
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发表时间:
2014-11
期刊:
影响因子:
--
通讯作者:
Konduri GG
中科院分区:
文献类型:
--
作者:
Cohen SS;Powers BR;Lerch-Gaggl A;Teng RJ;Konduri GG
Persistent pulmonary hypertension of the newborn (PPHN) is associated with increased risk of neuro-developmental impairments. Whether relative fetal hypoxia during evolution of PPHN renders the fetal brain vulnerable to perinatal brain injury remains unclear. We hypothesized that in utero ductal constriction, which induces PPHN also impairs cerebral angiogenesis. Fetal lambs with PPHN induced by prenatal ligation of the ductus arteriosus were compared to gestation matched twin controls. Freshly collected or fixed brain specimens were analyzed by immunohistochemistry, Western blot analysis, and RT-PCR. Cortical capillary density was decreased in PPHN lambs compared to controls (Glut-1, Isolectin B-4 and Factor VIII, n=6, p<0.05). Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels were decreased in cortical cell lysates of PPHN lambs. PPHN increased angiopoetin-1 (Ang-1) and tyrosine-protein kinase receptor (Tie-2) protein expression while angiopoetin-2 (Ang-2) protein levels were decreased (n=6, p<0.05). PPHN did not change mRNA levels of these proteins significantly (n=6). PPHN decreased cortical capillary density in fetal lamb brain. PPHN decreased the expression of proteins involved in angiogenesis. These findings suggest that PPHN is associated with impaired cortical angiogenesis.
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影响因子:
56.9
作者:
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者:
Ratcliffe, PJ
DOI:
10.1016/s0165-3806(01)00220-6
发表时间:
2001-09-23
期刊:
DEVELOPMENTAL BRAIN RESEARCH
影响因子:
--
作者:
Chow, J;Ogunshola, O;Madri, JA
通讯作者:
Madri, JA
影响因子:
64.8
作者:
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者:
Ratcliffe, PJ
影响因子:
8.9
作者:
Lai, JCK;Tranfield, EM;McManus, BM
通讯作者:
McManus, BM
影响因子:
3.3
作者:
Chen, X.;Threlkeld, S. W.;Cummings, E. E.;Juan, I.;Makeyev, O.;Besio, W. G.;Gaitanis, J.;Banks, W. A.;Sadowska, G. B.;Stonestreet, B. S.
通讯作者:
Stonestreet, B. S.