Associated inflammation or increased flow-mediated shear stress, but not pressure alone, disrupts endothelial caveolin-1 in infants with pulmonary hypertension.
Associated inflammation or increased flow-mediated shear stress, but not pressure alone, disrupts endothelial caveolin-1 in infants with pulmonary hypertension.
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DOI：
10.4103/2045-8932.105038
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发表时间：
2012-10-01
影响因子：
2.6
通讯作者：
Mathew, Rajamma
中科院分区：
文献类型：
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作者：
Dereddy, Narendra;Huang, Jing;Mathew, Rajamma
内皮细胞小窝蛋白-1损失是肺动脉高压（PH）的一个重要特征;小窝蛋白-1的救援废除实验PH。最近的研究表明，在人类PH的内皮细胞小窝蛋白-1损失是其次是增强表达的小窝蛋白-1在平滑肌细胞（SMC）与随后的新生内膜形成。为了评估肺高压婴儿中小窝蛋白-1的表达，我们检查了现有的临床病史、血流动力学数据以及从先天性心脏病（CHD，n = 8）和肺部疾病（n = 9）婴儿中获得的肺活检/尸检标本中小窝蛋白-1、PECAM-1、vWF和平滑肌α-肌动蛋白的表达。CHD组肺动脉血流量增加，肺动脉内皮细胞caveolin-1和PECAM-1表达减少; vWF表达增加，SMC caveolin-1表达增加。在没有PH的情况下，增加或减少肺血流量并没有破坏内皮小窝蛋白-1，PECAM-1，或vWF;也没有任何增强的表达小窝蛋白-1在SMC。在肺疾病+ PH组，窖蛋白-1，PECAM-1和vWF在7名婴儿中保存良好，重要的是，这些动脉中的SMC没有表现出窖蛋白-1表达增强。两名患有相关炎症性疾病的婴儿表现出内皮小窝蛋白-1和PECAM-1的丢失;另外vWF的丢失伴随着SMC中小窝蛋白-1的表达增强。因此，相关的流动诱导的剪切应力或炎症，而不是单独的肺动脉压升高，破坏内皮小窝蛋白-1。随后的vWF损失，表明广泛的内皮损伤与SMC中小窝蛋白-1的表达增强有关，这可能使疾病恶化。
Endothelial caveolin-1 loss is an important feature of pulmonary hypertension (PH); the rescue of caveolin-1 abrogates experimental PH. Recent studies in human PH suggest that the endothelial caveolin-1 loss is followed by an enhanced expression of caveolin-1 in smooth muscle cells (SMC) with subsequent neointima formation. In order to evaluate caveolin-1 expression in infants with PH, we examined the available clinical histories, hemodynamic data, and the expression of caveolin-1, PECAM-1, vWF, and smooth muscle alpha-actin in the lung biopsy/autopsy specimens obtained from infants with congenital heart disease (CHD, n = 8) and lung disease (n = 9). In CHD group, PH associated with increased pulmonary blood flow exhibited loss of endothelial caveolin-1 and PECAM-1 in pulmonary arteries; additional vWF loss was associated with enhanced expression of caveolin-1 in SMC. In the absence of PH, increased or decreased pulmonary blood flow did not disrupt endothelial caveolin-1, PECAM-1, or vWF; nor was there any enhanced expression of caveolin-1 in SMC. In Lung Disease + PH group, caveolin-1, PECAM-1, and vWF were well preserved in seven infants, and importantly, SMC in these arteries did not exhibit enhanced caveolin-1 expression. Two infants with associated inflammatory disease exhibited loss of endothelial caveolin-1 and PECAM-1; additional loss of vWF was accompanied by enhanced expression of caveolin-1 in SMC. Thus, associated flow-induced shear stress or inflammation, but not elevated pulmonary artery pressure alone, disrupts endothelial caveolin-1. Subsequent vWF loss, indicative of extensive endothelial damage is associated with enhanced expression of caveolin-1 in SMC, which may worsen the disease.