Project Grant R35HL176438

Award Date 8/1/25
Completion Date 4/30/32
Dollars Obligated $1.1M
Federal Grant Program
93.837
Assistance Type
Project Grant
Place of Performance
Los Angeles, CA 90095, USA
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This $1,102,500 Project Grant awarded by the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) will support research at the University of California, Los Angeles (UCLA) to address persistent problems in the field of intravascular triglyceride metabolism. The key focus areas include:

  1. Identifying sequences in apolipoprotein A5 (apoA5) that are important for suppressing the activity of the ANGPTL3/8 complex, and using that knowledge to develop therapeutics to preserve lipoprotein lipase (LPL) levels in capillaries and reduce atherogenic lipoprotein levels.

  2. Investigating whether ANGPTL3/8-mediated LPL detachment from cells results from LPL unfolding, and whether the ANGPTL3/8 complex preferentially detaches LPL from the glycocalyx of capillary endothelial cells.

  3. Determining through X-ray crystallography whether apoC2 activates LPL by opening its lid, and defining the transcriptional basis for heterogeneity in LPL and GPIHBP1 expression in endothelial cell subsets.

The research, which builds on the project team's prior discoveries, aims to transform understanding of intravascular lipolysis and uncover new strategies for preventing coronary heart disease. The project period runs from August 1, 2025 to April 30, 2032.

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