Current Research:

Hypertriglyceridemia remains an independent risk factor for the development of cardiovascular disease. Recently, a protein that plays a significant role in triglyceride metabolism was discovered by comparative sequence analysis of the mouse and human genomes. ApoAV, a 366 amino acid protein synthesized by the liver, is the only apoprotein to have been discovered by comparative sequence analysis. It was found to be located down-stream of the AI/CIII/AIV gene cluster on human chromosome 11q23. Mice overexpressing human apoAV display a 50-70% decrease in plasma triglyceride levels, while knock-out mice lacking apoAV resulted in a 4 fold increase of plasma triglycerides.

There are two hypotheses for the function of apoAV. One possibility is that apoAV operates at the intravascular level, to stimulate triglyceride hydrolysis. Recent in-vitro studies have shown increased free fatty acid release by proteoglycan-bound lipoprotein lipase in the presence of apoAV. An additional hypothesis is that apoAV functions intracellularly, to decrease triglyceride production or secretion. ApoAV contains a signal peptide that directs it toward the secretory pathway; however, plasma levels of this protein are low in comparison to other apolipoproteins. The concentration of apoAV is 0.1% the concentration of apoAI. This is one characteristic of apoAV that would support an intracellular function. Due to apoAV’s role in the regulation of triglyceride metabolism, this protein has the potential to be targeted therapeutically in the treatment of hypertriglyceridemia.

Presentations and Awards:

Oral Presentation:

Blade, A.  The Role of ApoAV in Triglyceride Metabolism.  South East Lipid Research Conference. October 3, 2006.  Callaway Gardens, Pine Mountain, GA.

Publications:

Mohler PJ, Zhu MY, Blade AM, Ham AJ, Shelness GS, Swift LL. Identification of a novel isoform of microsomal triglyceride transfer protein. J Biol Chem. 2007 Sep 14;282(37):26981-8.