Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute Hantavirus Pulmonary Syndrome.
Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute Hantavirus Pulmonary Syndrome.
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DOI：
10.1155/2012/674360
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发表时间：
2012
影响因子：
2.2
通讯作者：
Mackow E
中科院分区：
文献类型：
--
作者：
Gavrilovskaya I;Gorbunova E;Koster F;Mackow E
汉坦病毒肺综合征的特征是血管通透性、缺氧和急性肺水肿。血管内皮生长因子（VEGF）是由缺氧诱导的，有效地诱导血管通透性，并与高海拔诱导的肺水肿有关。汉坦病毒改变了β3整合素的正常调节，β 3整合素限制VEGF定向的渗透性，汉坦病毒感染的内皮细胞对VEGF的透化作用反应过度。然而，VEGF在HPS患者急性肺水肿中的作用尚不清楚。在这里，我们回顾性评估VEGF水平肺水肿液（PEF），血浆，血清和PBMC从31 HPS患者。与对照组相比，HPS患者PEF中的VEGF升高，在致命HPS病例的PEF样本中观察到最高水平。在住院的前五天，PBMC样本中的VEGF水平最高，在恢复期间降低。PEF和PBMC VEGF水平显著升高与HPS患者中观察到的急性肺水肿和HPS疾病严重程度一致。我们观察到体外膜肺氧合后严重HPS疾病幸存者的VEGF水平显著降低。这些发现表明HPS期间患者的VEGF水平的重要性，支持VEGF反应参与HPS发病机制，并建议靶向VEGF反应作为潜在的治疗方法。
Hantavirus pulmonary syndrome is characterized by vascular permeability, hypoxia, and acute pulmonary edema. Vascular endothelial growth factor (VEGF) is induced by hypoxia, potently induces vascular permeability, and is associated with high-altitude-induced pulmonary edema. Hantaviruses alter the normal regulation of β3 integrins that restrict VEGF-directed permeability and hantavirus infected endothelial cells are hyperresponsive to the permeabilizing effects of VEGF. However, the role of VEGF in acute pulmonary edema observed in HPS patients remains unclear. Here we retrospectively evaluate VEGF levels in pulmonary edema fluid (PEF), plasma, sera, and PBMCs from 31 HPS patients. VEGF was elevated in HPS patients PEF compared to controls with the highest levels observed in PEF samples from a fatal HPS case. VEGF levels were highest in PBMC samples during the first five days of hospitalization and diminished during recovery. Significantly increased PEF and PBMC VEGF levels are consistent with acute pulmonary edema observed in HPS patients and HPS disease severity. We observed substantially lower VEGF levels in a severe HPS disease survivor after extracorporeal membrane oxygenation. These findings suggest the importance of patients' VEGF levels during HPS, support the involvement of VEGF responses in HPS pathogenesis, and suggest targeting VEGF responses as a potential therapeutic approach.