The researchers found that mice engineered without the Akt1 gene and fed a high cholesterol diet had many more signs of aortic atherosclerosis compared to their littermates. And, surprisingly, their coronary lesions were similar to humans, say the scientists.

About 20 percent of the mice died spontaneously, perhaps due to an acute heart attack, said William Sessa, senior author of the study, professor of pharmacology, and director of Yale's vascular biology and therapeutics program.

Atherosclerosis is a chronic inflammatory response in arterial walls, in large part due to deposits of lipoproteins ”which are plasma proteins that carry cholesterol and triglycerides. The "hardening" or "furring" of the arteries is caused by plaque formation.

In the vascular wall, Akt plays an important role in regulating the development of endothelial cells, which line the entire circulatory system, from the heart to the smallest capillary. Endothelial cells play an important role in regulating blood pressure, in blood clotting, in plaque formation in the arteries, and in formation of new blood vessels.

The major finding of this study is that an absence of Akt1 aggravates atherosclerotic lesions, promotes coronary atherosclerosis, and may be a model of acute coronary syndromes, Sessa said. Specific activation of Akt1 may provide a therapeutic approach to decrease formation of lesions in the arterial wall and promote plaque stabilization to prevent an acute heart attack.

One concern, he said, is that specific drugs are being developed to inhibit Akt in cancer patients to reduce progression of tumors, and that these drugs may also promote hardening of the arteries.

yale/

Fatty acids like DHA are considered "essential" fatty acids because the body cannot make them from other sources and must obtain them through diet. Years of research have shown that DHA is the most abundant essential fatty acid in the brain, Cole said, and that it is critical to fetal and infant brain development. Studies have also linked low levels of DHA in the brain to cognitive impairment and have shown that lower levels may increase oxidative stress in the brains of Alzheimer's patients.

Based on the positive results, the National Institutes of Health is currently conducting a large-scale clinical trial with DHA in patients with established Alzheimer's disease. For those patients, Cole said, it may be too late in the disease's progression for DHA to have much effect. But he is hopeful that the NIH will conduct a large-scale prevention clinical trial using fish oil at the earliest stages of the disease ” particularly because it is unlikely that a pharmaceutical company will do so, since fish oil in pill form is readily available and inexpensive.

Still to be determined, he said, "is what the optimal dose should be. It could be that a smaller amount might be helpful, especially in a place like the south of France, where people are already on a Mediterranean diet."

Here in the United States, though, where fish consumption is not very high, the dose may need to be higher.

"There's a deficiency of DHA to begin with," Cole said, "and this may contribute to the low LR11 seen in many Alzheimer's patients."

ucla/