Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep
Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep
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DOI：
10.1152/ajplung.00256.2014
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发表时间：
2014-12-01
影响因子：
4.9
通讯作者：
Abman, Steven H.
中科院分区：
文献类型：
--
作者：
Dodson, R. Blair;Morgan, Matthew R.;Abman, Steven H.
新生儿持续性肺动脉高压（PPHN）是一种临床综合征，其特征是由于肺血管生长、结构和张力的改变而导致肺血管阻力高。PPHN主要被认为是一种小肺动脉（PA）疾病，但近端血管僵硬已被证明是与肺动脉高压（PH）相关的其他疾病发病率和死亡率的重要预测指标。本研究的目的是表征实验性PPHN的主PA （MPA）刚度，并确定MPA的生物力学变化与细胞外基质（ECM）含量和胶原蛋白和弹性蛋白纤维取向的变化之间的关系。从对照组和PPHN胎羊模型中分离MPAs，采用平面双轴试验测量血管周向和轴向的刚度。将测试标本固定用于血管壁ECM成分胶原蛋白和弹性蛋白的组织学评估。与对照组相比，PPHN羊的MPAs增加了机械刚度（P < 0.05），改变了ECM重塑。本构数学模型和组织学表明，与对照动脉相比，PPHN血管对弹性蛋白的贡献较小，对胶原纤维接合的作用更大。我们得出结论，暴露于慢性血流动力学应激妊娠晚期胎羊增加近端PA僵硬和改变ECM重塑。我们推测近端PA僵硬进一步导致实验性PPHN右心室阻抗增加，从而导致出生时肺循环的异常过渡。
Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characterize main PA (MPA) stiffness in experimental PPHN and to determine the relationship of altered biomechanics of the MPA with changes in extracellular matrix (ECM) content and orientation of collagen and elastin fibers. MPAs were isolated from control and PPHN fetal sheep model and were tested by planar biaxial testing to measure stiffness in circumferential and axial vessel orientations. Test specimens were fixed for histological assessments of the vascular wall ECM constituents collagen and elastin. MPAs from PPHN sheep had increased mechanical stiffness (P < 0.05) and altered ECM remodeling compared with control MPA. A constitutive mathematical model and histology demonstrated that PPHN vessels have a smaller contribution of elastin and a greater role for collagen fiber engagement compared with the control arteries. We conclude that exposure to chronic hemodynamic stress in late-gestation fetal sheep increases proximal PA stiffness and alters ECM remodeling. We speculate that proximal PA stiffness further contributes to increased right ventricular impedance in experimental PPHN, which contributes to abnormal transition of the pulmonary circulation at birth.