Searching for a successful HDL-based treatment strategy

• ApoA-I mimetic peptides were initially thought to work in plasma.
• Surprisingly, the peptides were found to work in small intestine.
• The peptides lower small intestine lysophosphatidic acid levels.
• Lowering small intestine lysophosphatidic acid levels lowers plasma levels.
• Lowering lysophosphatidic acid levels decreases inflammation & cell proliferation.

Despite strong evidence that HDL-cholesterol levels predict atherosclerotic events in a population, attempts at using an HDL-based treatment strategy have not yet been successful. Most of the efforts to date have focused on raising plasma HDL-cholesterol levels. This brief review focuses on a different strategy, which is based on the use of 18-amino acid apoA-I mimetic peptides. The story of these peptides spans decades and illustrates the remarkable complexity of HDL-based treatment strategies, but suggests that such a strategy may still be successful.