Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism
Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism
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DOI：
10.1152/ajplung.00074.2012
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发表时间：
2012-08-01
影响因子：
4.9
通讯作者：
Irwin, David C.
中科院分区：
文献类型：
--
作者：
Buehler, Paul W.;Baek, Jin Hyen;Irwin, David C.
Buehler PW, Baek JH, Lisk C, Connor I, Sullivan T, Kominsky D, Majka S, Stenmark KR, Nozik-Grayck E, Bonaventura J, Irwin DC。游离血红蛋白诱导肺血管疾病：炎症机制的证据。[J] .中国生物医学工程学报，2016,31(4):387 - 398。首次发表于2012年6月22日；doi: 10.1152 / ajplung.00074.2012。无细胞血红蛋白（Hb）暴露可能是肺动脉高压（PAH）发展的致病介质，当合并慢性缺氧时，PAH恶化和血管重构的潜力可能更加明显。我们假设Hb可能作为促氧化剂、炎症和一氧化氮（NO）清除剂共同促进缺氧驱动的多环芳烃。使用可编程微泵技术，我们将雄性Sprague-Dawley大鼠暴露在室内空气或缺氧条件下，每天12或30毫克Hb，持续3、5和7周。观察血压、心输出量、右心室肥厚、肺血管重构等指标。此外，测定氧化应激标志物、NO生物利用度和炎症反应。Hb增加肺动脉（PA）压力，肺血管壁硬化，右心肥厚，具有时间和剂量依赖性。Hb诱导血浆氧化应激标志物（丙二醛和4-羟基壬烯醛）适度增加，no生物利用度无变化，肺ICAM蛋白表达增加。抗氧化剂Tempol治疗可减轻hb诱导的肺动脉壁增厚，但不能减轻PA压力或ICAM表达。啮齿动物长期暴露于低血浆Hb浓度（范围= 3-10 μ M）长达7周，通过炎症和较小程度的Hb介导氧化诱导肺血管疾病。Tempol对hb诱导的肺血管疾病的衰减有适度的影响。在该模型中，NO的生物利用度是最不重要的。
Buehler PW, Baek JH, Lisk C, Connor I, Sullivan T, Kominsky D, Majka S, Stenmark KR, Nozik-Grayck E, Bonaventura J, Irwin DC. Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism. Am J Physiol Lung Cell Mol Physiol 303: L312-L326, 2012. First published June 22, 2012; doi:10.1152/ajplung.00074.2012.-Cell-free hemoglobin (Hb) exposure may be a pathogenic mediator in the development of pulmonary arterial hypertension (PAH), and when combined with chronic hypoxia the potential for exacerbation of PAH and vascular remodeling is likely more pronounced. We hypothesized that Hb may contribute to hypoxia-driven PAH collectively as a prooxidant, inflammatory, and nitric oxide (NO) scavenger. Using programmable micropump technology, we exposed male Sprague-Dawley rats housed under room air or hypoxia to 12 or 30 mg per day Hb for 3, 5, and 7 wk. Blood pressure, cardiac output, right ventricular hypertrophy, and indexes of pulmonary vascular remodeling were evaluated. Additionally, markers of oxidative stress, NO bioavailability and inflammation were determined. Hb increased pulmonary arterial (PA) pressure, pulmonary vessel wall stiffening, and right heart hypertrophy with temporal and dose dependence in both room air and hypoxic cohorts. Hb induced a modest increase in plasma oxidative stress markers (malondialdehyde and 4-hydroxynonenal), no change in NO bioavailability, and increased lung ICAM protein expression. Treatment with the antioxidant Tempol attenuated Hb-induced pulmonary arterial wall thickening, but not PA pressures or ICAM expression. Chronic exposure to low plasma Hb concentrations (range = 3-10 mu M) lasting up to 7 wk in rodents induces pulmonary vascular disease via inflammation and to a lesser extent by Hb-mediated oxidation. Tempol demonstrated a modest effect on the attenuation of Hb-induced pulmonary vascular disease. NO bioavailability was found to be of minimal importance in this model.