Journal
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
Volume 17, Issue 2, Pages 156-160Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MED.0b013e328337278b
Keywords
ATP-binding-membrane-cassette transporter A1; cholesteryl ester transfer protein; endothelial lipase; secretory phospholipase A(2); serum amyloid A
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Funding
- NIH [PO1HL086670]
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Purpose of review Inflammation and the concomitant acute phase response induce marked changes in the lipoprotein profile, particularly the high-density lipoprotein (HDL) fraction. The present review describes the transfer proteins and lipases that remodel HDL and regulate its plasma levels, discusses the changes occurring in their activities during inflammation, and the influence of this altered remodeling on HDL function. The review will also discuss the contribution of the ATP-binding-membrane-cassette transporters to the protective actions of HDL. Recent findings Studies using different models showed that remodeling of acute phase HDL in vitro generates pre-beta migrating particles capable of cholesterol efflux. Induction of the acute phase response in humans resulted in a reduction of HDL phospholipids without a change in HDL-cholesterol. However, the capacity of HDL to promote cholesterol efflux ex vivo was impaired. Studies with ATP-binding-membrane-cassette transporter A1 and ATP-binding-membrane-cassette transporter G1 knockout mice demonstrated anti-inflammatory roles for these transporters by virtue of reducing cell-membrane-free cholesterol and lipid raft content, thus attenuating proinflammatory signaling pathways. Summary It is well known that HDL has anti-inflammatory properties that are diminished during inflammation. Acute phase HDL contains serum amyloid A that can be liberated during remodeling by cholesteryl ester transfer protein and secretory phospholipase A(2), or other inflammatory factors. The ability of serum amyloid A and apolipoprotein A-I to promote cholesterol efflux may confer protective effects during the acute phase response.
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