Hematopoietic stem cell transplantation alters susceptibility to pulmonary hypertension in Bmpr2-deficient mice.
Hematopoietic stem cell transplantation alters susceptibility to pulmonary hypertension in Bmpr2-deficient mice.
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DOI：
10.1177/2045894018801642
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发表时间：
2018-10
影响因子：
2.6
通讯作者：
Morrell NW
中科院分区：
文献类型：
--
作者：
Crosby A;Toshner MR;Southwood MR;Soon E;Dunmore BJ;Groves E;Moore S;Wright P;Ottersbach K;Bennett C;Guerrero J;Ghevaert C;Morrell NW
越来越多的证据表明，肺动脉高压（PAH）患者表现出骨髓（BM）和造血祖细胞异常。此外，PAH与骨髓增生性疾病相关。我们以前已经证明，低剂量的脂多糖（LPS）是一个有力的刺激PAH的发展背景下的遗传PAH小鼠模型的BMPR 2功能障碍。我们假设造血祖细胞可能在这个模型中驱动疾病。为了验证这一假设，我们在野生型（Ctrl）和杂合Bmpr 2无效（Mut）小鼠之间进行了BM的过继转移。在BM重建后16周，将小鼠暴露于低剂量慢性LPS（0.5mg/kg，每周三次，持续6周）。对小鼠进行右心导管插入术，并取出组织进行组织学检查。在慢性LPS给药后，接受Mut BM的对照小鼠发展为PAH，而接受对照BM的Mut小鼠受到保护免于PAH。BM组织学显示接受Mut BM的对照小鼠中巨核细胞增加，循环血小板增加。这些结果表明，造血干细胞区室参与Mut小鼠对PAH的易感性。结果提出了造血干细胞移植可能是遗传形式PAH的潜在治疗策略的可能性。
Increasing evidence suggests that patients with pulmonary arterial hypertension (PAH) demonstrate abnormalities in the bone marrow (BM) and hematopoietic progenitor cells. In addition, PAH is associated with myeloproliferative diseases. We have previously demonstrated that low-dose lipopolysaccharide (LPS) is a potent stimulus for the development of PAH in the context of a genetic PAH mouse model of BMPR2 dysfunction. We hypothesized that the hematopoietic progenitor cells might be driving disease in this model. To test this hypothesis, we performed adoptive transfer of BM between wild-type (Ctrl) and heterozygous Bmpr2 null (Mut) mice. Sixteen weeks after BM reconstitution, mice were exposed to low-dose chronic LPS (0.5 mg/kg three times a week for six weeks). Mice underwent right heart catheterization and tissues were removed for histology. After chronic LPS dosing, Ctrl mice in receipt of Mut BM developed PAH, whereas Mut mice receiving Ctrl BM were protected from PAH. BM histology demonstrated an increase in megakaryocytes and there was an increase in circulating platelets in Ctrl mice receiving Mut BM. These findings demonstrate that the hematopoietic stem cell compartment is involved in the susceptibility to PAH in the Mut mouse. The results raise the possibility that hematopoietic stem cell transplantation might be a potential treatment strategy in genetic forms of PAH.
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影响因子：
2.6
作者：
Yang X;Long L;Reynolds PN;Morrell NW
通讯作者：
Morrell NW
HE 和免疫组织化学染色评价大鼠股骨脱钙技术
影响因子：
--
作者：
Liu H;Zhu R;Liu C;Ma R;Wang L;Chen B;Li L;Niu J;Zhao D;Mo F;Fu M;Brömme D;Zhang D;Gao S
通讯作者：
Gao S
DOI：
10.1161/atvbaha.107.141200
发表时间：
2007-05-01
影响因子：
8.7
作者：
Morty, Rory E.;Nejman, Bozena;Eickelberg, Oliver
通讯作者：
Eickelberg, Oliver
影响因子：
20.3
作者：
Asosingh, Kewal;Farha, Samar;Erzurum, Serpil C.
通讯作者：
Erzurum, Serpil C.
影响因子：
2.7
作者：
Beppu, H;Kawabata, M;Miyazono, K
通讯作者：
Miyazono, K