Intravenous Injection of Apo A-V Reconstituted High-Density Lipoprotein Reduces Blood Triglycerides in Mouse Model

Results of a study conducted on a mouse model of hypertriglyceridemia (HTG) showed that injections of the plasma protein apolipoprotein A-V (apo A-V) dramatically lowered levels of triglycerides (TGs) in the blood.

Investigators at the Children's Hospital Oakland Research Institute (CA, USA) worked with two different lines of mice that had been genetically engineered to develop HTG. One line lacked the gene for apo A-V, while the other carried the normal apo A-V gene.

Purified apo A-V was combined with phospholipid in the form of a reconstituted high-density lipoprotein (rHDL), and the complex was injected into the mice. Results published in the October 21, 2010, online edition of the journal Arteriosclerosis, Thrombosis, and Vascular Biology revealed that the mice lacking the apo A-V gene experienced a 60% reduction in plasma TG concentration after four hours. The authors attributed this decline to enhanced catabolism/clearance of very-low-density lipoprotein (VLDL), where VLDL TG and cholesterol were reduced by about 60%. Apo A-V that associated with VLDL after injection was also rapidly cleared.

In contrast to the apo A-V deficient mice, injection of rHDL into the other HTG line had no effect on plasma TG levels, and apo A-V remained associated with plasma VLDL.

"We wanted to know if we could lower triglyceride levels in mice lacking apo A-V by simply reintroducing apo A-V into the bloodstream, because if so, it could be a very worthwhile avenue for trying to reduce triglyceride levels in human beings,” said senior author Dr. Trudi Forte, staff scientist at Children's Hospital Oakland Research Institute . "We were gratified to see that the triglyceride level went down, and it continued to go down by 87% over an eight-hour period.”

"What we have here is the potential for apo A-V to have some therapeutic benefit to human beings in terms of reducing triglyceride levels and helping prevent heart disease,” said 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.”

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Children's Hospital Oakland Research Institute