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Damien Morton dmorton at bitfurnace.com
Sat Apr 9 05:43:37 PDT 2016


Atherosclerosis is an inflammatory disease linked to elevated blood
cholesterol concentrations. Despite ongoing advances in the prevention and
treatment of atherosclerosis, cardiovascular disease remains the leading
cause of death worldwide. Continuous retention of apolipoprotein
B–containing lipoproteins in the subendothelial space causes a local
overabundance of free cholesterol. Because cholesterol accumulation and
deposition of cholesterol crystals (CCs) trigger a complex inflammatory
response, we tested the efficacy of the cyclic oligosaccharide
2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol
solubility in preventing and reversing atherosclerosis. We showed that CD
treatment of murine atherosclerosis reduced atherosclerotic plaque size and
CC load and promoted plaque regression even with a continued
cholesterol-rich diet. 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. Because CD treatment in humans is safe and CD
beneficially affects key mechanisms of atherogenesis, it may therefore be
used clinically to prevent or treat human atherosclerosis.

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