Hyperlipidemia, a condition with high levels of fats circulating in the bloodstream, is a known risk factor for various cardiovascular and metabolic disorders. While the Western diet often contributes to high levels of lipids such as cholesterol and triglycerides, over-production of the body's own lipoproteins can lead to hyperlipidemia, independent of food intake.
In a discovery that may pave the way towards new treatments for high cholesterol, researchers led by M. Mahmood Hussain, PhD, Professor of Cell Biology at SUNY Downstate Medical Center, found that a regulatory RNA molecule interferes with the production of lipoproteins and, in a mouse model, reduces hyperlipidemia and atherosclerosis. Their study was published recently in the online edition of Nature Medicine.
Dr. Hussain, whose laboratory focuses on molecular mechanisms of intestinal lipoprotein assembly, says, "High plasma lipid and lipoprotein levels are a risk factor for atherosclerosis, and lowering plasma lipid levels is a national goal. While current medications and changes in diet can be effective, cardiovascular disease remains the number one cause of death in the United States, and additional approaches to decrease lipid levels are needed."
In their Nature Medicine article, Dr. Hussain and colleagues note that "overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia." They demonstrate that microRNA-30c (miR-30c), a genetic regulator, interacts with MTP and induces its degradation, leading to reductions in MTP activity, the production of lipoproteins, plasma lipids, and atherosclerosis. This molecule also reduces lipid synthesis independently of MTP thereby avoiding complications associated with drug therapies aimed at lowering lipoprotein production.
The authors conclude that a medication mimicking miR-30c could potentially be effective in reducing hyperlipidemia in humans.
This work was supported in part by U.S. National Institutes of Health grants R01DK046900, from the National Institute of Diabetes and Digestive and Kidney Diseases, and R01HL095924, from the National Heart, Lung and Blood Institute.
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