News Release

Protein injection shows promise in lowering elevated triglycerides

American Heart Association rapid access journal report

Peer-Reviewed Publication

American Heart Association

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.

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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.

Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.heart.org/corporatefunding.

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