CHORI Researchers Find That ApoA-V Protein Reduces High Triglyceride Levels in Mice, Decreases Heart Disease

Newswise — An exciting new study conducted by Children’s Hospital Oakland Research Institute (CHORI) scientists identified that an injection of the protein apolipoprotein (apo)A-V may reduce high triglyceride levels in the blood and subsequently reduce coronary artery disease. Like cholesterol, elevated levels of triglyceride, a fat in the blood, is associated with the increased risk of heart disease—the number one cause of death in the United States.

The study, led by CHORI scientist Trudy Forte, PhD, will be featured in the December 2010 print issue of the American Heart Association journal, Arteriosclerosis, Thrombosis, and Vascular Biology (available online October 21, 2010).

Although apoA-V is found only in very low concentrations in the blood, it has a very big impact on maintaining normal triglyceride levels. Studies have shown that knockout mice genetically engineered to lack apoA-V have extremely high triglyceride levels, while mice genetically engineered to have an excess of apoA-V have extremely low triglyceride levels.

“We wanted to know if we could lower triglyceride levels in mice lacking apoA-V by simply reintroducing apoA-V into the bloodstream, because if so, it could be a very worthwhile avenue for trying to reduce triglyceride levels in human beings,” said Dr. Forte.

By combining apoA-V with phospholipid to produce an apoA-V reconstituted high density lipoprotein (rHDL), Dr. Forte and her team were able to inject apoA-V directly into the bloodstream of the mice – and significantly reduce triglyceride levels.

“We were gratified to see that the triglyceride level went down, and it continued to go down by 87 percent over an eight-hour period.”

Although further studies are required, this new research demonstrates that apoA-V may just hold the key to reducing triglycerides in humans in a clinical setting.

“What we have here is the potential for apoA-V to have some therapeutic benefit to human beings in terms of reducing triglyceride levels and helping prevent heart disease,” says Dr. Forte. “ To move that potential another step closer to reality, we need to confirm similar results in other mouse models with elevated triglyceride levels.” Dr. Forte and her colleagues hope to confirm the results in continued studies throughout the next year.

About Children’s Hospital & Research Center OaklandChildren’s Hospital & Research Center Oakland is Northern California’s only independent not-for-profit regional medical center for children. Children’s Hospital Oakland is a national leader in many pediatric specialties and sub-specialties including hematology/oncology, neonatology, cardiology, orthopedics, sports medicine, and neurosurgery. The hospital is one of only two solely designated California Level 1 pediatric trauma centers with the largest pediatric inpatient critical care unit in the region. Children’s Hospital has 190 licensed beds, 201 hospital-based physicians in 30 specialties, more than 2,700 employees, and an annual operating budget of more than $350 million. Children’s is also a premier teaching hospital with an outstanding pediatric residency program and a number of unique pediatric subspecialty fellowship programs.

Children’s research program, Children’s Hospital Oakland Research Institute (CHORI), is internationally renowned for taking state-of-the-art basic and clinical research and translating it into interventions for treating and preventing human diseases. CHORI has 300 members of its investigative staff, a budget of about $50 million, and is ranked among the nation’s top 10 research centers in National Institutes of Health funding to children’s hospitals. For more information, go to www.childrenshospitaloakland.org and www.chori.org.

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Arteriosclerosis, Thrombosis, and Vascular Biology