Good Cholesterol Gone Bad

New research has detected a molecular process that makes high-density lipoprotein (HDL), or the “good cholesterol,” become dysfunctional. Rather than protect the heart, HDL would promote inflammation, and harden and clog the arteries. Cleveland Clinic researchers found that Apolipoprotein A1 (apoA1), a structural molecule that transfers cholesterol out of artery walls and other parts of the body to the liver for removal, can become oxidized by myeloperoxidase (MPO) in the artery wall. In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function and instead contributes to the development of coronary artery disease. After understanding the dysfunctional process, the scientists tested the blood of 627 cardiology patients to determine that higher levels of dysfunctional HDL increase the patient’s risk for cardiovascular disease. Traditional HDL cholesterol tests can’t detect dysfunctional HDL as they only show the amount of cholesterol each HDL particle is carrying, not its function. This finding may help explain why drug treatments that raise HDL levels have failed to improve cardiovascular health in pharmaceutical trials. The study suggests that efforts to improve heart disease by targeting HDL should be revisited. Reference: Huang Y, DiDonato J, Levison B, et al. An abundant dysfunctional apolipoprotein A1 in human atheroma. Nature Medicine. 2014. doi:10.1038/