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A zebrafish model of a rare genetic disease has revealed an unexpected regulatory pathway for cholesterol absorption and processing. The findings, reported in the Journal of Molecular Medicine, were "quite surprising and have the potential to teach us about the basic physiology of cholesterol management," said Ela Knapik, M.D., associate professor of Medicine and Cell and Developmental Biology.

The researchers, Eicke Latz at the University of Bonn and colleagues, followed up on the parents' hypothesis and found that in mice, cyclodextrin indeed blocked plaque formation, melted away plaques that had already formed in arteries, reduced atherosclerosis-associated inflammation, and revved up cholesterol metabolism-even in rodents fed cholesterol-rich diets. In petri dish-based tests, the researchers found that the drug seemed to have the same effects on human cells and plaques.

This case study describes a visit by "Naomi" to her physician, who upon seeing Naomi's bloodwork decides to prescribe her a cholesterol-lowering agent, a statin. The case discusses (1) the prevalence of non-communicable diseases such as atherosclerosis, which can lead to strokes and heart disease; (2) circulating lipoprotein particles including LDL and HDL, differentiating between which is a risk factor for heart disease and which is protective;  (3) the pathway for cholesterol synthesis; (4) the evidence demonstrating that statins inhibit the enzyme HMG-CoA reductase, which is the committed step for cholesterol synthesis; and (5) the kinetic mechanism by which statins inhibit the enzyme. Students examine and interpret data from radioactive tracer and enzyme kinetics studies. The case ends with another visit by Naomi to her physician, who reexamines her bloodwork after she has been taking a statin for six months. Students are asked to determine whether the drug was effective for Naomi and, if not, what changes could be made to her regimen. The case was originally written for use in a survey of biochemistry course for upper level undergraduates.

Six years ago, Yale University's Stephen Stearns and colleagues took advantage of a long-running study in Framingham, Massachusetts, to assess whether the effects of natural selection could be discerned among the people in the multigenerational study population. Over the last seven decades, public-health researchers have been monitoring the residents of Framingham, noting their vital statistics as well as blood sugar and cholesterol levels to understand the factors that lead to heart disease. As the initial group of research subjects got older, the study started to include their children, and then their grandchildren. The records provide a unique view of the health of a segment of the American population since 1948.