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Targeted Expression of Heme Oxygenase-1 Prevents the Pulmonary Inflammatory and Vascular Responses to Hypoxia
Tohru Minamino, Helen Christou, Chung-Ming Hsieh, Yuxiang Liu, Vijender Dhawan, Nader G. Abraham, Mark A. Perrella, S. Alex Mitsialis and Stella Kourembanas
Proceedings of the National Academy of Sciences of the United States of America
Vol. 98, No. 15 (Jul. 17, 2001), pp. 8798-8803
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3056248
Page Count: 6
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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.
Proceedings of the National Academy of Sciences of the United States of America © 2001 National Academy of Sciences