Atherosclerotic plaque is a complex environment in which cholesterol, phospholipids, protein, and their oxidized molecules co-exist. Many of these oxidized species have been shown to undergo auto-oxidation generating downstream stable lipid carbonyls and their cyclized products which, independently or complexed with proteins, may have plaque destabilizing effects. Reverse cholesterol transport involving the efflux and transport of cholesterol and phospholipids from peripheral tissues to the liver for metabolism helps to maintain lipid homeostasis. The same process is also expected to reduce plaque burden and thereby cardiac incidents. High-density lipoprotein cholesterol (HDL) is crucial in this process. Through HDL mimetics, drugs that enhance functional HDL, dietary modifications, and exercise, we can achieve only 10–30% plaque burden. However, none of these molecules are reported to scavenge or quench oxidized forms of the trapped lipid moieties or their decomposition products. Molecules that scavenge/quench lipid carbonyls can prevent carbonyl adduct formation and may provide additional benefits. Improved plaque regression therefore could be possible with molecules that enhance functional HDL as well as scavenge lipid carbonyls.
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