Tomatoes engineered with mimic of good-cholesterol peptide benefit mice
February 20, 2013 § 1 Comment
Special tomatoes to stave off heart attacks and strokes? In a recent paper in the Journal of Lipid Research, a group of researchers describe a genetically engineered tomato that contains a protein that helps stave off atherosclerosis, the buildup of plaque in arteries that leads to heart attacks and strokes.
ApoA-I mimetic therapy is currently one way to treat atherosclerosis. Apolipoprotein (apo)A-I, which has 243 amino acids, is the main component in high-density lipoprotein, also known as good cholesterol. In animal models and humans, infusions of apoA-I have been associated with improvements in atherosclerosis. But given its length, it’s an expensive protein to produce and has to be given intravenously.
Mimics of apoA-I have been produced with only 18 to 26 amino acids. They don’t have sequence similarities with apoA-I but they bind lipids in the same way. Srinivasa Reddy and Alan Fogelman at the David Geffen School of Medicine at the University of California Los Angeles, along with their colleagues, have been studying an apoA-I mimetic peptide called 4F.
4F has been demonstrated in animal models to reduce inflammation, atherosclerosis and other disease processes associated with inflammation. The animal studies spawned two clinical trials. Data from the trials led the investigators to conclude that 4F was most effective when taken orally and processed in the small intestine.
But the problem was that the necessary oral dose was high. “The 4F peptide can only be made by chemical synthesis,” explains Reddy. “The cost of producing enough 4F peptide by chemical synthesis to achieve efficacy prevented this from being pursued as a therapy in humans.”
So the investigators began a search for a peptide that didn’t require extensive chemical synthesis and could be produced by genetic engineering. They came up with another peptide called 6F and decided to see if they could produce it in tomatoes. “We wanted to produce the peptide in a plant that could be eaten without cooking because we felt that cooking the peptide might denature it,” says Fogelman. “The tomato was a convenient and tasty choice.”
The investigators genetically engineered tomatoes to produce the 6F peptide, freeze-dried the fruit, ground them into a powder and added the powder to a high-fat, high-cholesterol Western diet for mice. “We found that, some hours after feeding the peptide, it was still intact in the small intestine,” says Reddy. “Markers of inflammation in the blood were significantly reduced, HDL-cholesterol and HDL function were significantly improved, and atherosclerosis of the aorta was significantly reduced.”
Put together, the investigators say, the work demonstrates that tomatoes engineered to produce an apoA-I mimic could potentially be used as-is to reduce inflammation and atherosclerosis without having to extract and purify the peptide from the plant.