The next weapon against heart disease could be a compound that is currently used to make drugs more soluble.
In atherosclerosis, plaques containing crystallized cholesterol clog up blood vessels. Eicke Latz of the University Hospital in Bonn, Germany, and his colleagues tested a compound called 2-hydroxypropyl-β-cyclodextrin, which increases the solubility of cholesterol, to see whether it reduced the plaques. They found that plaques shrank in atherosclerotic mice that had consumed cyclodextrin (blood vessel pictured left, cholesterol crystals in white), compared with plaques in the blood vessels of untreated animals (pictured right).
The drug bound to and dissolved the cholesterol crystals. It also increased cholesterol metabolism in immune cells called macrophages, which usually contribute to atherosclerosis by triggering inflammation in response to excess cholesterol. Cyclodextrin reprogrammed the cells in plaques, leading to increased transport of the dissolved cholesterol away from the plaques, and reducing harmful inflammation. Some of the same effects were seen in human plaque samples treated with the compound.
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Molecule melts away cholesterol. Nature 532, 151 (2016). https://doi.org/10.1038/532151c