Heme oxygenase (HO) catalyzes the first and rate-limiting step in the oxidative degradation of heme to bilirubin. While HO-2 is constitutively expressed, HO-1 is highly induced by heme, metal ions, cytokines, and agents causing oxidative stress such as LPS during gram negative sepsis. The PI's laboratory has shown that HO-1 induction may play a role in protection against oxidative stress in an in vivo model of septic shock and MOSF. In this proposal the investigators propose to utilize HO-1 transgenic and knockout mice to test their hypothesis that HO-1 plays a critical role in providing protection against oxidative stress. Specifically, they propose to 1) generate and identify transgenic mice overexpressing HO-1 selectively in the endothelial and vascular smooth muscle cells in the vascular wall, 2) determine the physiological, biochemical and cellular responses of HO-1 overexpressing transgenic mice in a murine model of septic shock and MOSF, 3) apply HO-1 knockout mice to this sepsis model, and 4) determine the mechanism(s) by which HO-1 induction protects against oxidative stress.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Lung Biology and Pathology Study Section (LBPA)
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Korpela, Jukka K
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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