High-density lipoprotein and the acute phase response

Abstract

Purpose of review Inflammation and the concomitant acute phase response induce marked changes in the lipoprotein profile, particularly the HDL fraction. This 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 ABC transporters to the protective actions of HDL. Recent findings Studies using different models showed that remodeling of AP HDL in vitro generates pre-beta migrating particles capable of cholesterol efflux. Induction of the APR 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 ABCA1 and ABCG1 knock-out mice demonstrated anti-inflammatory roles for these transporters by virtue of reducing cell membrane free cholesterol and lipid raft content, thus attenuating pro-inflammatory signaling pathways. Summary It is well known that HDL has anti-inflammatory properties which are diminished during inflammation. AP HDL contains SAA which can be liberated during remodeling by CETP and sPLA2, or other inflammatory factors. The ability of SAA and apoA-I to promote cholesterol efflux may confer protective effects during the APR.

Proteomic diversity of high density lipoproteins: our emerging understanding of its importance in lipid transport and beyond

“…The importance of this process has been demonstrated by in vivo models of RCT showing that genetic lowering of plasma HDL decreases the appearance of macrophage-derived cholesterol in the feces ( 36 ). HDL also has well documented antioxidative properties and has been shown to prevent oxidative modifi cation of LDL, thus reducing macrophage foam-cell generation in the by guest, on May 12, 2018 www.jlr.org Downloaded from enhanced cholesterol delivery from HDL may allow the adrenals to better produce anti-infl ammatory glucocorticoids in response to stress. As it is known to bind vascular proteoglycans ( 48 ), SAA may also tether HDL in the vascular matrix, thereby preventing RCT and inhibiting oxidation ( 49 ).…”

“…by guest, on May 12, 2018 www.jlr.org Downloaded from artery disease (CAD) ( 23,74,75 ). They identifi ed several proteins that were enriched in the CAD patients, including apoE, apoC-IV, PON1, complement C3, and apoA-IV, all involved in vascular infl ammation.…”

Dusty Punch Cards and an Eternal Enigma: High-Density Lipoproteins and Atherosclerosis

“…Whether the function of HDL as an acceptor of cellular cholesterol is impaired in the acute phase is not entirely clear [59]. Because LDL-C, apolipoprotein B, and triglycerides remained virtually unaffected in the Dal-OUTCOMES study, the study may indeed provide clues to the utility of isolated manipulation of HDL-C.…”

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

“…Inflammation and the concomitant acute phase response induce marked changes in the lipoprotein profile [52]. Thus, in portal hypertensive-rat, hepatic steatosis is associated with the plasmatic increase of low density lipoprotein (LDL) and lipopolysaccharide binding protein (LBP) as well as reduction of high-density lipoproteins (HDL) [43,45].…”

“…It is also accepted that acute phase proteins, particularly serum amyloid A, inhibits the ability of acute phase HDL to serve as an acceptor for cellular cholesterol efflux. This promotes the removal of excess cholesterol from macrophages, as well as increases the availability of cellular free cholesterol and thereby, increases the development of atherosclerotic lesions [52,61].…”