Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

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
Stable URL: http://www.jstor.org/stable/3056248
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Targeted Expression of Heme Oxygenase-1 Prevents the Pulmonary Inflammatory and Vascular Responses to Hypoxia
Preview not available

Abstract

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.

Page Thumbnails

  • Thumbnail: Page 
8798
    8798
  • Thumbnail: Page 
8799
    8799
  • Thumbnail: Page 
8800
    8800
  • Thumbnail: Page 
8801
    8801
  • Thumbnail: Page 
8802
    8802
  • Thumbnail: Page 
8803
    8803