Epidemiological studies show plasma concentrations of bilirubin, formed by biliverdin reductase A (BVRA), to inversely associate with the risk of cardiovascular and metabolic diseases. However, a causative link between bilirubin and these diseases remains to be established.
Lab models to assess the role of bilirubin in cardiometabolic diseases indicate that BVRA deficiency has no measurable effect on plasma lipids and antioxidants. However, the lab models have higher concentrations of plasma lipid hydroperoxides and their erythrocyte peroxiredoxin 2 is more oxidized, indicative of the presence of systemic oxidative stress.
Lab models to assess the role of bilirubin in cardiovascular disease have indicated that BVRA/bilirubin attenuates atherogenesis and plaque destabilisation. However, BVRA deficiency in combination with a high fat diet increases hepatic concentrations of cholesterol and triglycerides, indicating that BVRA/bilirubin deficiency enhances hepatic steatosis, but not insulin resistance.
This project investigates the detailed mechanisms underlying the above-described protective effects of bilirubin on cardiovascular and metabolic diseases. This may provide novel protective strategies against these diseases.