[Frontiers in Bioscience 16, 2372-2388, June 1, 2011]

Protective role of heme oxygenase-1 against inflammation in atherosclerosis

William Durante

Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Anti-Inflammatory Actions of HO-1
4. Role of Inflammation in Atherosclerosis
5. Protective Role of HO-1 against Inflammation in Atherosclerosis
6. Therapeutic Approaches Targeting HO-1 in Vascular Inflammation
7. Summary and Perspectives
8. Acknowledgements
9. References

1. ABSTRACT

Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting step in the metabolism of free heme into equimolar amounts of ferrous iron, carbon monoxide (CO), and biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. HO-1 has recently been identified as a promising therapeutic target in the treatment of vascular inflammatory disease, including atherosclerosis. HO-1 represses inflammation by removing the pro-inflammatory molecule heme and by generating CO and the bile pigments, biliverdin and bilirubin. These HO-1 reaction products are capable of blocking innate and adaptive immune responses by modifying the activation, differentiation, maturation, and/or polarization of numerous immune cells, including endothelial cells, monocytes/macrophages, dendritic cells, T lymphocytes, mast cells, and platelets. These cellular actions by CO and bile pigments result in diminished leukocyte recruitment and infiltration, and pro-inflammatory mediator production within atherosclerotic lesions. This review highlights the mechanisms by which HO-1 suppresses vascular inflammation in atherosclerosis, and explores possible therapeutic modalities by which HO-1 and its reaction products can be employed to ameliorate vascular inflammatory disease.