But as it turns out, the HDL picture is not so simple. To begin with, some patients with even high levels of HDL show no improvement in their protection from cardiovascular disease. Equally perplexing at first was the discovery of a particular mutation of HDL known as ApoA-1 Milano. Individuals bearing this mutation had low levels of good cholesterol, yet their HDL proved highly effective in preventing atherosclerosis.

According to Nelson, such apparent contradictions to the accepted role of HDL cholesterol are due to a range of protein subclasses that exist within the makeup of HDL "What starts out as just HDL," said Nelson, "turns into several different proteins, each of which, in turn, can exist in a of number different molecular forms."

Tai notes that the outcome of their project could have a significant impact on cardiovascular medicine. "In the prevention of heart disease today, precise risk assessment is critical to the decision making process," said Tai. The higher the risk an individual faces, the more aggressive treatment is. What we look at currently is the average risk for the group. With the kind of data that will be generated from this study, we may be able to divide patients into smaller and smaller groups with more precise risk estimates. This will lead to much more individualized treatment."

The Biodesign-NUHS collaboration is a first step along the path to a better understanding of HDL's role in human health, promoting earlier diagnoses and more effective treatments. "There's 100 years of biology leading up to what we are starting to see," Nelson notes. "We have a better set of eyes now."

Source: Arizona State University