Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia
AUTOR(ES)
Minamino, Tohru
FONTE
The National Academy of Sciences
RESUMO
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-α signaling. We have previously proposed a crucial role for heme oxygenase-1 (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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=37515Documentos Relacionados
- Heme oxygenase-1 and carbon monoxide in pulmonary medicine
- Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice
- Heme oxygenase-1 induction modulates hypoxic pulmonary vasoconstriction through upregulation of ecSOD
- Ketamine-induced hepatoprotection: the role of heme oxygenase-1
- Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia.
