How Genetic Mutation Causes Coronary Atherosclerosis

About eleven million Americans suffer from coronary atherosclerosis. The number one killer in the US will likely claim 500,000 lives this year alone. Unhealthy eating habits, obesity, smoking and high cholesterol levels are among the risk factors listed for this disease. Even a genetic predisposition has been suspected before. Now scientists at Yale School of Medicine have proven that a mutant gene indeed is at the root of the disease and greatly promotes coronary atherosclerosis.

Coronary atherosclerosis is a thickening or hardening of the arteries due to a build-up of plaque. The plaque is a mixture of cholesterol and fatty substances as well as calcium, fibrin, and other cellular waste products. The plaque attaches itself to the inner lining of the artery and thereby reduces the elasticity of the artery's wall. In the long run the artery walls will thicken and harden. This narrowing of the arteries reduces the blood flow through the particular arteries. People suffering from the disease are at risk of experiencing among others heart attack, stroke, abdominal angina, bowel infarction, and gangrene.

Treatment for disease usually includes a change in diet and other habits like smoking, alcohol consumption, and exercise. Cholesterol lowering and blood pressure controlling drugs are widely used. Furthermore, surgical options are available to prevent likely deathly outcomes like heart attacks and strokes. Treatment varies from case to case, yet oftentimes patients face a lifelong dependency on drugs to prevent further plaque deposits on the artery walls.

The study conducted at the Yale School of Medicine in Cell Metabolism offers a new treatment alternative for this deadly disease. The scientists studied mice whose Akt1 gene was removed through genetic engineering. These mice were provided with a high cholesterol diet. The mice developed aortic atherosclerosis to a greater extent than the mice in the control group. Amazingly, they also showed coronary lesions very similar to those of human beings. According to the scientists Akt1 is a gene that aids in the regulation of endothelial cells in the artery walls. These endothelial cells on the other hand are needed in the formation of new blood vessels as well as for the control of blood pressure, blood clotting, and plaque formation. Without Akt1 the number of atherosclerotic lesions, and therefore the risk of developing coronary atherosclerosis, dramatically increases.

This discovery opens up new avenues for drug development for the treatment of coronary atherosclerosis. Drugs that activate Akt1 within the patient's body will help to decrease the formation of lesions and promote plaque stabilization in an attempt to prevent heart attacks and strokes. There is also concern that drugs currently in development for cancer patients designed to inhibit Akt1 functions in order to stop tumor growth may ultimately promote coronary atherosclerosis.