Bilirubin acts as a multi-potent guardian of cardiovascular integrity: more than just a radical idea

Bilirubin, a potentially toxic catabolite of heme and indicator of hepato-biliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion (I-R) injury. These effects attenuate multiple stages of the atherosclerotic process, in addition to protecting the heart d...