Oct. 22, 2010 Injecting a protein that helps break down triglycerides may someday help treat an inherited form of high triglycerides, according to a new study in Arteriosclerosis, Thrombosis, and Vascular Biology, an American Heart Association journal.
Triglyceride is a type of fat in the blood. Elevated levels in the blood -- hypertriglyceridemia -- have been linked to coronary artery disease. In the study, researchers tested a new compound in mice genetically altered to be deficient in a protein called apolipoprotein (apo)A-V, which causes them to have high blood levels of triglycerides. ApoA-V boosts the efficiency of lipoprotein lipase, an enzyme needed to break down triglycerides. The active compound consists of apoA-V complexed with phospholipid to form a reconstituted high density lipoprotein (HDL). The researchers administered the compound in the mice intravenously.
"We asked a simple question: If you just inject apoA-V into these mice that are lacking apoA-V and have very high levels of triglyceride, will it go down?" said Trudy Forte, Ph.D., study senior author and a scientist at Children's Hospital Oakland Research Institute in California. "We were very gratified to see that it went down, and it continued to do so over an eight-hour period."
By the end of the treatment, triglycerides had dropped about 87 percent.
However, in engineered mice lacking a protein called GPIHBP1, which also leads to very high triglycerides, the apoA-V injection didn't lower levels.
Intravenous apA-V may have a therapeutic benefit in humans with severely elevated triglycerides due to genetic changes that affect their levels of apoA-V, the researchers said.
Co-authors are: Xiao Shu, Ph.D.; Lisa Nelbach, Ph.D.; Michael M. Weinstein, Ph.D.; Braydon L. Burgess, M.S.; Jennifer A. Beckstead, M.S.; Stephen G. Young, M.D.; and Robert O. Ryan, Ph.D. Author disclosures and sources of funding are on the manuscript.
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- X. Shu, L. Nelbach, M. M. Weinstein, B. L. Burgess, J. A. Beckstead, S. G. Young, R. O. Ryan, T. M. Forte. Intravenous Injection of Apolipoprotein A-V Reconstituted High-Density Lipoprotein Decreases Hypertriglyceridemia in apoav-/- Mice and Requires Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1. Arteriosclerosis, Thrombosis, and Vascular Biology, 2010; DOI: 10.1161/ATVBAHA.110.210815
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