Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice

Abstract

Supplementary key words bradykinin • cholesterol • foam cells • high density lipoprotein • histamine • lipoproteins • mast cells • serotoninVascular endothelium is a semipermeable barrier that regulates the solute composition of interstitial fl uids by an ultrafi ltration process of various blood components ( 1 ). Such a sieving effect also determines the passage through the endothelium of the various types of lipoproteins, which are the largest blood solutes. It was an early observation in hypercholesterolemic rabbits that the arterial infl ux of plasma HDL, LDL, and VLDL decreases linearly with the logarithm of the diameter of the lipoprotein particles ( 2 ). Studies in humans and other mammalian species also indicated that the fl ux of LDL from plasma into the arterial wall depends not only on its plasma concentration but also on its permeability at the plasma-arterial wall interface ( 3 ).Accumulation of excess cholesterol in cytoplasmic lipid droplets of macrophages in the arterial intima is a primary event in atherosclerosis. Accordingly, an efficient control of the cholesterol pool in the arterial foam cells is essential to prevent progression of the disease or even to induce its regression. In general, control of cellular cholesterol balance is partially achieved by the transfer of cellular cholesterol from peripheral body compartments to the liver and ultimately to the gut for its fecal excretion along a pathway that is known as the reverse cholesterol transport (RCT) ( 4 ). Effl ux of cellular

The role of the lymphatic system in cholesterol transport

“…When vascular permeability is increased, influx of HDL into interstitial fluid is enhanced, and the rate of RCT is increased. The result supports the observation of the importance of passive HDL transport ( Kareinen et al, 2015 ). Adenoviral overexpression of PLTP in hepatocytes generates larger particle size (<7.1 nm but larger than lipid-free ApoA1; Ji et al, 2014 ) and also increases atherosclerotic lesion size in PLTP overexpressing ApoE deficient mice ( Zhang et al, 2014 ), although the causal relationship between PLTP and CVD is still under debate ( Vergeer et al, 2010 ; Kim et al, 2015 ).…”

Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture

“…Moreover, we found apoA-I in wider areas in more degenerated and lipidcontaining sIAs walls, which may be due to inflammation and increased permeability of the walls. Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice (42). Since apoA-I is namely involved in clearance of accumulated lipids, our finding raises the possibility that the cholesterol efflux function of apoA-I in the sIA wall may be impaired.…”

Membrane cholesterol depletion as a trigger of Nav1.9 channel‐mediated inflammatory pain

“…In plasma membrane compartment, cholesterol is subsequently converted to cholesteryl ester and transported to the liver for elimination. In favor of this hypothesis, histamine and bradykinin, two inflammatory mediators, have been shown to enhance both transendothelial penetration of HDL into skin interstitial fluid and transfer of cholesterol into serum compartment (Kareinen et al , ). The second mechanism relies on enhanced production of ROS, nitric oxide (NO) synthesis, and the interplay of these molecules (Salvemini et al , ; Wang et al , ; Khattab, ; Gamper & Ooi, ).…”