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Pharmacology & Therapeutics

Pharmacology & Therapeutics

IF: 12
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Cyclodextrins: Potential therapeutics against atherosclerosis

Published:1 October 2020 DOI: 10.1016/j.pharmthera.2020.107620 PMID: 32599008
Maryam Mahjoubin-Tehran , Petri T. Kovanen , Suowen Xu , Tannaz Jamialahmadi , Amirhossein Sahebkar

Abstract

Atherosclerosis is an inflammatory disease resulting from subendothelial accumulation of lipoprotein-derived cholesterol in susceptible arterial segments, ultimately leading to the formation of clinically significant atherosclerotic plaques. Despite significant advances in the treatment of atherosclerosis, atherosclerotic cardiovascular diseases remain the leading cause of death and disabilities worldwide. Accordingly, there is an urgent need for novel therapies. Cyclodextrins are cyclic oligosaccharides produced from many sources of starch by enzymatic degradation. The frequently used cyclodextrins are α-, β-, and γ-cyclodextrins, which are composed of six, seven, and eight glucose moieties, respectively. Especially β-cyclodextrin can entrap hydrophobic compounds, such as cholesterol, into its hydrophobic cavity and form stable inclusion complexes with cholesterol. This inherent affinity of cyclodextrins has been exploited to extract excess cholesterol from cultured cells, as well as intra- and extracellular cholesterol stores present in atherosclerotic lesions of experimental animals. Accordingly, cyclodextrins could be considered as potentially effective therapeutic agents for the treatment of atherosclerosis. In this review, we address recent advances and the current status of the development of cyclodextrins and provide an update of the latest in vitro and in vivo experiments that pave the way to clinical studies. The emerging therapeutic opportunities by using cyclodextrins could aid us in our efforts to ultimately eradicate the residual risk after other cholesterol-lowering pharmacotherapies, and also reduce the associated burden of premature deaths due to atherosclerotic cardiovascular diseases.

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