HEME OXYGENASE-1 AND SEPSIS USING TRANSGENIC MICE

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from the applicant's abstract): 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.