ScienceDaily (Mar. 4, 2007) — High levels of good cholesterol (high density lipoprotein (HDL)) are associated with protection from cardiovascular disease, which remains the leading cause of death in the United States. But what exactly makes HDL so “good” for us?

In an attempt to answer this question researchers from the University of Washington, Seattle, have determined exactly what proteins are contained within HDL and have identified a number of surprises; further analysis of which might provide new understanding of the mechanisms by which HDL provides protection from cardiovascular disease and lead to the development of both accurate indicators of disease risk and new treatments for this disease.

In the study, which appears in the March issue of the Journal of Clinical Investigation, Jay Heinecke and colleagues isolated HDL from both healthy individuals and individuals with coronary artery disease (CAD) and assessed the protein content of these large complexes by mass spectrometry.

As well as the expected proteins involved in lipid metabolism, HDL from healthy individuals contained several proteins involved in the innate immune response (including complement proteins), several serine proteinase inhibitors, and many acute-phase inflammatory proteins. By contrast, HDL from patients with CAD contained high levels of the protein apoE, which is involved in lipoprotein transport.

As discussed in the accompanying commentary by Muredach Reilly and Alan Tall, this study supports “the concept that HDL plays a role in innate immunity and in the regulation of proteolytic cascades involved in inflammatory and coagulation processes.” and “could eventually help in the development of biomarkers to predict the outcome of interventions that alter HDL levels and functions.”

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