A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

Scott J Cameron,Annemarie F Swaim,Craig N Morrell,Charles J Lowenstein,Clare Bao,Annabelle Rodriguez,John Calvert

doi:10.1371/journal.pone.0144372

Abstract

High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis.

Highlights

high density lipoprotein (HDL) plays an important role in maintaining cholesterol homeostasis through the process of reverse cholesterol transport, mediating the centripetal movement of cholesterol from peripheral tissues to the liver and excretion into bile [1]
These data suggest that HDL-3, or a component of HDL-3, inhibits endothelial Weibel-Palade body degranulation
Purified apolipoproteins and HDL-3 are not toxic to endothelial cells at their IC50% for inhibition of exocytosis (Fig 3E) and, apoA-I appears to promote cell viability even under resting conditions. These results suggest that apoA-I is a functionally significant component of HDL-3 that most potently inhibits endothelial exocytosis compared to the other apolipoproteins, and so we directed most of our remaining studies toward apo-AI.to the other apolipoproteins, and so we directed most of our remaining studies toward apo-AI

Summary

Introduction

HDL plays an important role in maintaining cholesterol homeostasis through the process of reverse cholesterol transport, mediating the centripetal movement of cholesterol from peripheral tissues to the liver and excretion into bile [1]. Clinical studies have shown that plasma levels of HDL and its major apolipoprotein component apoA-I are inversely related to cardiovascular events [2, 3]. Animal studies show that HDL and apoA-I are anti-atherogenic [4,5,6]. The major cardiovascular benefit of HDL was originally attributed to its role in one particular aspect of reverse cholesterol transport, transferring cholesterol from macrophages in atherosclerotic lesions to the liver [7, 8]. PLOS ONE | DOI:10.1371/journal.pone.0144372 December 17, 2015

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