Heme Oxygenase-1 Deficiency Accelerates Formation of Arterial Thrombosis Through Oxidative Damage to the Endothelium, Which Is Rescued by Inhaled Carbon Monoxide

• DOI: 10.1161/circresaha.107.158998
• Publication Date: 2007-09-21T01:14:59Z
• Authors: Andrea L. True; Michelle Olive; Manfred Boehm; Hong San; Randal J. Westrick; Nalini Raghavachari; Xiuli Xu; Edward G. Lynn; Michael N. Sack; Peter J. Munson; Mark T. Gladwin; Elizabeth G. Nabel
• Keywords: HMOX1

Heme oxygenase (HO)-1 (encoded by Hmox1) catalyzes the oxidative degradation of heme to biliverdin and carbon monoxide. HO-1 is induced during inflammation stress protect tissues from damage. Because intravascular thrombosis forms at sites tissue inflammation, we hypothesized that protects against arterial oxidant stress. To investigate direct function on thrombosis, used photochemical-induced vascular injury in Hmox1-/- Hmox1+/+ mice. mice developed accelerated, occlusive thrombus compared with mice, detected several mechanisms accounting for this antithrombotic effect. First, endothelial cells arteries were more susceptible apoptosis denudation, leading platelet-rich microthrombi subendothelium. Second, factor, von Willebrand Factor, reactive oxygen species significantly elevated consistent cell damage loss. Third, following transplantation donor bone marrow into recipients subsequent injury, observed rapid receiving marrow. Fourth, inhaled monoxide administration rescued prothrombotic phenotype Fifth, using a transcriptional analysis tissue, found determined response specific effects cycle regulation, coagulation, redox homeostasis. These data provide genetic evidence protective role Induction may be beneficial prevention associated inflammation.