HDL biology
A review identifies CETP as a key enzyme liberating serum amyloid A during acute-phase HDL remodeling (Curr Opin Endocrinol Diabetes Obes 2010)
Original title: High-density lipoprotein and the acute phase response
This review describes the transfer proteins and lipases that remodel HDL and regulate its plasma levels, and how their activities change during inflammation and the acute phase response, along with the resulting effects on HDL function. Studies show that acute-phase HDL remodeled in vitro generates pre-beta migrating particles capable of cholesterol efflux, while inducing the acute phase response in humans reduces HDL phospholipids without changing HDL cholesterol, though HDL cholesterol efflux capacity ex vivo is impaired; ABCA1 and ABCG1 knockout mice show anti-inflammatory roles for these transporters via reducing cell-membrane free cholesterol and lipid raft content. Acute phase HDL contains serum amyloid A that can be liberated during remodeling by cholesteryl ester transfer protein (CETP) and secretory phospholipase A2, and the ability of serum amyloid A and apolipoprotein A-I to promote cholesterol efflux may confer protective effects during the acute phase response.
Original abstract
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 A2, 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.