Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia
Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia
复制标题
DOI：
10.1073/pnas.161272598
复制
发表时间：
2001-07-17
影响因子：
11.1
通讯作者：
Kourembanas, S
中科院分区：
文献类型：
--
作者：
Minamino, T;Christou, H;Kourembanas, S
慢性缺氧可引起肺动脉高压，并伴有肺小动脉壁平滑肌细胞增生和基质沉积。我们在此证明，缺氧还可在血管壁结构改变之前诱导肺内明显的炎症反应。缺氧的促炎作用是通过诱导不同的细胞因子和趋化因子介导的，并且不依赖于肿瘤坏死因子-cu信号传导。我们先前已经提出血红素加氧酶-l（HO-1）在保护心肌细胞免受缺氧应激中的关键作用，并且已经在组织损伤模型中报道了HO-1的有效抗炎特性，因此，我们建立了在肺中组成型表达HO-1的转基因小鼠，并将它们暴露于慢性缺氧，HO-1转基因小鼠免受缺氧诱导的肺部炎症以及高血压和血管壁肥大的发展。值得注意的是，HO-1转基因小鼠中促炎细胞因子和趋化因子的缺氧诱导被抑制。我们的研究结果表明，HO-1活性的酶产物作为缺氧诱导的血管收缩和促炎途径的抑制剂具有重要的保护功能。
Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles, We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia is mediated by the induction of distinct cytokines and chemokines and is independent of tumor necrosis factor-cu signaling, We have previously proposed a crucial role for heme oxygenase-l (HO-1) in protecting cardiomyocytes from hypoxic stress, and potent anti-inflammatory properties of HO-1 have been reported in models of tissue injury, We thus established transgenic mice that constitutively express HO-1 in the lung and exposed them to chronic hypoxia, HO-1 transgenic mice were protected from the development of both pulmonary inflammation as well as hypertension and vessel wall hypertrophy induced by hypoxia. Significantly, the hypoxic induction of proinflammatory cytokines and chemokines was suppressed in HO-1 transgenic mice. Our findings suggest an important protective function of enzymatic products of HO-1 activity as inhibitors of hypoxia-induced vasoconstrictive and proinflammatory pathways.