Lowering cholesterol by blocking ACAT2. Cholesterol is found in every cell of the body and helps to digest fats, strengthen cell membranes and make hormones. Although cholesterol has many important functions, excess cholesterol can build up on artery walls and cause atherosclerosis leading to heart attack and stroke. Therefore, a great deal of research has gone into finding ways of lowering the body's cholesterol levels. Now, scientists at the Gladstone Institute of Cardiovascular Disease in San Francisco have discovered a new mechanism through which cholesterol levels could be controlled.
Cholesterol exists either as a free molecule or as an esterified molecule in cells.
Based on the hypothesis that ACAT2 is the main enzyme responsible for esterification in the small intestine and liver, and that esterification is extremely important in the absorption and use of cholesterol, Robert Farese and colleagues developed a strain of mice lacking the gene for ACAT2. When fed a high fat, high cholesterol diet, these mice differed from normal mice because they did not develop hypercholesterolemia or gallstones-an indicator of high blood cholesterol levels. The scientists discovered that the mice lacking ACAT2 were less able to absorb dietary cholesterol from the intestine than normal mice. If these findings extend to humans, then drugs that are able to block the actions of ACAT2 should prove to be a new treatment for conditions caused by high cholesterol. All treatments for cancer are based on the concept of exploiting the difference between cancerous and normal cells.