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    Straight from the heart

    Many scientists have started thinking beyond cholesterol. In fact, cholesterol is important for health (although a bad ration of LDL/HDL is a problem.)

    Lipids called ceramides may be better predictors of cardiovascular problems than cholesterol.

    ***

    To pin down her susceptibility to atherosclerosis, Vasile prescribed a test for substances Blendermann had never heard of: lipids called ceramides. Long overlooked, they are emerging as powerful alternatives to standard markers of heart disease risk such as LDL cholesterol. Blendermann’s score was moderately high, suggesting that compared with a person with a low score, she was more than twice as likely to suffer a cardiovascular event such as a heart attack. “It woke us up big time,” she says. “The ceramides told me the bigger story.” She began to take cholesterol-lowering drugs and overhauled her diet and exercise regime.


    Doctors and drug companies are also warming to the medical possibilities of ceramides. Blendermann is one of just a few thousand people in the United States to have undergone ceramide blood testing, which is only performed by the Mayo Clinic. But later this year, lab testing giant Quest Diagnostics will start to offer the analysis, potentially making it available to many more patients.


    The first drugs specifically designed to lower ceramide levels are also on the horizon, with at least two companies hoping to begin clinical trials within the next year or so. And researchers are refining their picture of how these molecules, which account for less than 1% of the lipids in the body, exert such a powerful influence over our physiology. Ceramides are essential for a variety of cellular functions. But a stack of studies also implicates high levels of the molecules in heart disease and illnesses such as diabetes and fatty liver disease, suggesting they may cause havoc as well.


    “There is overwhelming evidence that [ceramides] are major driving forces for metabolic dysfunction,” says physiologist Philipp Scherer of the University of Texas Southwestern Medical Center. That makes them valuable for assessing patients’ odds of developing some chronic illnesses—and “an excellent predictor of cardiovascular risk,” says Jeff Meeusen, co-director of cardiovascular laboratory medicine at the Mayo Clinic.

    Still, the medical community has not embraced ceramides. Before that happens, cardiologists will have to accept an unfamiliar test and learn how to interpret the results alongside standard risk factors. And before patients start to receive ceramide-lowering drugs, developers will have to show that interfering with compounds fundamental to the body does more good than harm.


    UNTIL A LITTLE OVER 30 years ago, ceramides “were not on anyone’s radar screen,” says Yusuf Hannun, a lipidologist at Stony Brook University. The few researchers who did think about the molecules, which are found throughout the body, assumed they were metabolically inert. In 1993, Hannun and his colleagues performed one of the first studies that helped change that perception.


    The researchers wanted to find out how a specific immune system molecule spurs malignant cells to commit suicide, protecting against cancer. They discovered the molecule acts through ceramides, suggesting the lipids are important for conveying messages within cells. Soon afterward, a new technique called liquid chromatography-mass spectrometry revolutionized the study of the lipids. The technique, which can sort complex molecular mixtures, revealed that cells carry numerous ceramide varieties—mammals boast more than 200 types—and scientists have been trying to tease out the molecules’ functions ever since.
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