Potential atherosclerosis drug exhibits no harmful side-effects in liver

Researchers have developed and tested a synthetic atherosclerosis drug that can reduce the build-up of dangerous blood vessel plaques without producing the side-effect of fatty liver disease (which leads to its own set of problems like diabetes). The encouraging results of this study in mice could lead to a new type of drug to treat or even prevent atherosclerosis.

Targets of this drug, called DMHCA, are proteins called the Liver X Receptors (LXR). These proteins control a body's cholesterol levels by limiting the absorption of dietary cholesterol and by increasing the conversion of cholesterol into bile acids. Unfortunately, most LXR ligands also control fatty acid production, so therapeutic compounds that activate LXR also raise the levels of other fats, particularly in the liver.

DHMCA, though, had negligible effects of fat production in laboratory tests, so Dagmar Kratky and colleagues tested it in mice genetically engineered to be atherosclerotic. They found that compared to another experimental LXR drug (T0901317), DMHCA could significantly reduce the size of arterial lesions in the mice (45-48%) without increasing fat content in the liver or blood. Together, these results, appearing in the February Journal of Lipid Research, show much therapeutic promise.

From the article: "Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without inducing liver steatosis and hypertriglyceridemia," by Adelheid Kratzer, Marlene Buchebner, Thomas Pfeifer, Tatjana Becker, Georg Uray, Makoto Miyazaki, Shinobu Miyazaki-Anzai, Birgit Ebner, Prakash Chandak, Rajendra Kadam, Emine Calayir, Nora Rathke, Helmut Ahammer, Branislav Radovic, Michael Trauner, Gerald Hoefler, Uday Kompella, Guenter Fauler, Moshe Levi, Sanja Levak-Frank, Gerhard Kostner, and Dagmar Kratky

Article link: http://www.jlr.org/cgi/content/full/50/2/312

Corresponding Author: Dagmar Kratky, Institute of Molecular Biology & Biochemistry, Medical University of Graz, Austria; Tel: +43 316 380 7543; email: kratky@meduni-graz.at