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Abstract
Cholesterol esters, synthesized from cholesterol with long-chain fatty acids, are essential components of plasma lipoproteins and cell membranes that participate in various metabolic processes in the body. Cholesterol can be excreted through the cholesterol reverse transport (RCT) pathway when excessive cholesterol is produced in the extrahepatic cells, which is regulated by the liver X receptor (LXR) and its downstream regulators ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1) genes. Abnormal cholesterol metabolism is closely associated with the development of diabetic retinopathy (DR). However, the precise underlying mechanism of the RCT pathway in the pathogenesis of DR is still not fully understood. This review focused on cholesterol metabolism, with a particular emphasis on the RCT pathway and its correlation with the development of DR. Particular attention has been paid to the key regulators of the RCT pathway: LXR, ABCA1, and ABCG1 genes and their potential therapeutic targets in the management of DR.
Highlights
The association between abnormal lipid metabolism and microvascular complications of diabetes has received considerable attention recently
This review summarizes the recent progress on cholesterol metabolism abnormalities, emphasizing the association of the reverse cholesterol transport (RCT) pathway in the pathogenesis of diabetic retinopathy (DR)
Following liver X receptor (LXR) activation by an agonist, cholesterol efflux is promoted through the RCT pathway and is taken up by apoA-I and apoE to form new high-density lipoprotein (HDL) molecules, which enter the visceral liver for further transformation and/or decomposition [40]
Summary
The association between abnormal lipid metabolism and microvascular complications of diabetes has received considerable attention recently. The imbalance of the reverse transport (RCT) pathway of cholesterol under high glucose pathological conditions is a new focus of research becoming a hot topic. This review summarizes the recent progress on cholesterol metabolism abnormalities, emphasizing the association of the RCT pathway in the pathogenesis of diabetic retinopathy (DR). This novel research direction may lead to an insight into discovering biomarkers and molecular targets for tailored therapies.
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