Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus
Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus
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DOI：
10.1152/ajplung.00199.2002
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发表时间：
2003-05-01
影响因子：
4.9
通讯作者：
Abman, SH
中科院分区：
文献类型：
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作者：
Balasubramaniam, V;Le Cras, TD;Abman, SH
血小板衍生生长因子(PDGF)是一种强大的平滑肌细胞有丝分裂原，在慢性肺动脉高压(PH)的发生发展过程中可能参与了平滑肌的增殖。我们研究了胎龄124~128天(足月=147天)部分结扎动脉导管(DA)所致慢性宫内肥大(PH)羔羊PDGFα、β受体及其配体表达的变化。8天后，对PH动物全肺匀浆进行Western印迹分析，结果显示PDGFα和β受体蛋白比年龄匹配的对照组增加了一倍(P<；0.05)。肺组织中PDGF-A和PDGF-B的表达在PH组和对照组之间无明显差异。我们用NX1975处理PH动物，NX1975是一种选择性抑制PDGF-B的适配子，在DA结扎后向左肺动脉内注入7天。NX1975使小肺动脉肌性增厚减少47%(P<；0.05)，右室肥厚减少66%(P<；0.02)。肺血管内皮生长因子α和β受体在围产期PH中的表达增加，而NX1975减少了该模型中肺小动脉壁厚度和RVH的增加。我们推测PDGF信号通路参与围产期PH的结构性血管重塑，选择性抑制PDGF可能为慢性PH的治疗提供新的治疗策略。
Platelet-derived growth factor (PDGF) is a potent smooth muscle cell mitogen that may contribute to smooth muscle hyperplasia during the development of chronic pulmonary hypertension (PH). We studied changes in PDGF alpha- and beta-receptor and ligand expression in lambs with chronic intrauterine PH induced by partial ligation of the ductus arteriosus (DA) at gestational age 124-128 days (term = 147 days). Western blot analysis performed on whole lung homogenates from PH animals after 8 days of DA ligation showed a twofold increase in PDGF alpha- and beta-receptor proteins compared with age-matched controls (P < 0.05). Lung PDGF-A and -B mRNA expression did not differ between PH and control animals. We treated PH animals with NX1975, an aptamer that selectively inhibits PDGF-B, by infusion into the left pulmonary artery for 7 days after DA ligation. NX1975 reduced the development of muscular thickening of small pulmonary arteries by 47% (P < 0.05) and right ventricular hypertrophy (RVH) by 66% (P < 0.02). Lung PDGF α- and β-receptor expression is increased in perinatal PH, and NX1975 reduces the increase in wall thickness of small pulmonary arteries and RVH in this model. We speculate that PDGF signaling contributes to structural vascular remodeling in perinatal PH and that selective PDGF inhibition may provide a novel therapeutic strategy for the treatment of chronic PH.