Bilirubin metabolism and its role in atherosclerosis

Abstract

Hemoglobin is not an guiltless bystander of the pathophysiology in a number of atherosclerotic diseases. Heme, which is released from hemoglobin or other heme proteins, triggers various pathophysiological consequence, including heme stress as well as intracellular stress. Although heme serves key functions and is tightly controlled, high levels of free heme, which may occur in various pathophysiological conditions, are may hazardous via pro-oxidant, pro-inflammatory, and cytotoxic effects. Heme oxygenases are heat shock protein enzymes that use heme as a substrate and function as an essential antioxidant adaptive response by all human cells. A major function of heme oxygenases is clearance of heme that accumulate in tissues due to erythrocyte turnover. The potentially toxic free heme is converted by heme oxygenases into carbon monoxide, iron, and biliverdin, the latter of which is reduced to bilirubin. In literature the heme degradation pathway has been demonstrated to play a protective role against the development of atherosclerosis. Because growing evidence suggests that oxidative stress is involved in atherosclerosis. This review documents the roles of bilurubin in atherosclerosis and focuses on the clinical significance as a potential therapeutic target in atherosclerotic diseases, such as coronary artery disease.

Keywords

• Bilirubin,Atherosclerosis,Heme oxygenases,Oxidative stress,Cardiovascular diseases

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