An international team has now found that cyclodextrin (CD) dissolves cholesterol crystals and reduces atherosclerotic plaques. This is a promising therapeutic approach for treating atherosclerosis. Their find was published in Science Translational Medicine.
Cyclodextrin works by reprogramming macrophages so that they do not cause such a strong inflammatory response in blood vessels that contain cholesterol crystals. The cyclodextrin also dissolves cholesterol crystals so that the cholesterol can be excreted from the body in urine. The result is prevention of plaque formation and even atherosclerotic plaque reduction in mice.
Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport.
Furthermore, when researchers used cyclodextrin to treat biopsies of plaques from human carotid arteries, they found similar results.
The study points to cholesterol crystals as a target for treatment of atherosclerosis, meaning that using cyclodextrin to dissolve the crystals could affect how the disease is treated.
The original idea for the test of cyclodextrin came from Chris Hempel, an American mother whose twin daughters are affected by a rare illness called Niemann-Pick Type C disease, in which cholesterol accumulates in the body. The children are being treated with cyclodextrin with promising results.
Hempel read about previous research on cholesterol crystals conducted by senior researcher Eicke Latz from the University Hospital Bonn and his colleagues from the Center of Molecular Inflammation Research (CEMIR) at the Norwegian University of Science and Technology (NTNU) in Trondheim. She contacted Dr. Latz to suggest that they test cyclodextrin as a possible treatment for atherosclerosis.