In Dallas the two men began their collaborative research on the genetic factors that are responsible for high levels of cholesterol in the bloodstream. They compared the cells of normal persons with those of persons having familial hypercholesterolemia, which is an inherited tendency to get abnormally high blood cholesterol levels and, as a result, atherosclerosis and other circulatory ailments.
Brown and Goldstein were able to trace a genetic defect in the afflicted persons that resulted in their lacking or being deficient in cell receptors for low-density lipoproteins (LDL), which are the primary cholesterol carrying particles. Their research established that these cell receptors draw the LDL particles into the cells as a prelude to breaking them down, and thus remove them from the bloodstream. The two men also discovered that the cell capture of such lipoproteins inhibits the further production of new LDL receptors by the cells, thus explaining how high-cholesterol diets overwhelm the body's natural capacity for withdrawing cholesterol from the bloodstream.
Brown later collaborated with Goldstein in research to develop new
drugs effective in lowering blood cholesterol levels and in researching
the basic genetic code behind the LDL receptor. From 1977 he was professor
and director of the Center for Genetic Diseases in Dallas.
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