Although raising HDL is a major focus for many companies generating small molecule atherosclerosis therapies, the strategy has not yet led to clinical benefit. Researchers from the Cleveland Clinic reported last week in Nature Structural and Molecular Biology that they may have discovered the reason by identifying the site of dysfunction in HDL that inhibits the body's ability to fight cholesterol accumulation.

Using hydrogen-deuterium exchange mass spectrometry and computational modeling, they identified key structural features that are linked to maturing the HDL particle from its nascent discoidal form to a cholesterol-laden spherical form.