Disruption of cholesterol efflux by coxib medications and inflammatory processes: link to increased cardiovascular risk.
Atherosclerosis is a chronic progressive disease that is a major contributor to cardiac death. It is characterized by inflammation and cholesterol deposition in the arterial wall. Excess cholesterol accumulation occurs as a result of an imbalance between delivery and removal and leads to formation of lipid-laden foam cells. Removal of cholesterol through a process known as reverse cholesterol transport requires the coordinated functioning of a number of genes including the P450 27-hydroxylase and the adenosine triphosphate-binding cassette transporter A1 (ABCA1). Reverse cholesterol transport is a key defense against atheroma formation. This review discusses the role of inflammatory processes in impeding reverse cholesterol transport. Particular emphasis is placed on the disruption of cholesterol outflow observed in the presence of cyclooxygenase inhibitors in cultured monocytes/macrophages. These inhibitors, which are used clinically to relieve pain and inflammation, have been associated with increased risk of cardiovascular disease and myocardial infarction. We explore the relationship between suppression of reverse cholesterol transport and harmful cardiac effects of coxibs.
Reiss
Allison B
AB
Vascular Biology Institute, Department of Medicine, Winthrop-University Hospital, Mineola, NY, and Department of Medicine, NYU School of Medicine, New York, NY, USA. AReiss@winthrop.org
Anwar
Farah
F
Chan
Edwin S L
ES
Anwar
Kamran
K
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006801:Humans
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D052246:Cyclooxygenase 2 Inhibitors; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase