scholarly journals Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.

1993 ◽  
Vol 91 (2) ◽  
pp. 522-529 ◽  
Author(s):  
M C Cheung ◽  
A J Mendez ◽  
A C Wolf ◽  
R H Knopp
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Tangier Disease ◽  
Apolipoprotein A ◽  
Intracellular Cholesterol

Abstract 190: The Effect of Particle Size on Apolipoprotein A-I Exchange in Reconstituted and Human-derived High Density Lipoprotein Particles

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Mark S Borja ◽  
Lorena G Ortega-Guerrero ◽  
Michael N Oda
Keyword(s):  
Particle Size ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Density Lipoprotein ◽  
High Density ◽  
Size Exclusion ◽  
Paramagnetic Resonance ◽  
Size Dependent ◽  
Apolipoprotein A

Objective: The ability of high density lipoprotein (HDL) to promote cholesterol efflux from ATP binding cassette transporter A1 (ABCA1) is inversely associated with HDL particle size. The exchangeability of HDL’s primary protein constituent, apolipoprotein A-I (apoA-I), is positively correlated with cholesterol efflux capacity. However, it is unknown whether HDL particle size similarly affects the exchangeability of apoA-I. In this study, we investigated the effect of HDL particle size on the exchangeability of apoA-I on reconstituted (rHDL) and human-derived plasma HDL (pHDL) particles. Method and Results: Discoidal rHDL particles of well-defined size (17.0, 12.2, 9.6, 8.4 and 7.8 nm) were prepared from POPC and apoA-I by cholate dialysis and purified by size exclusion chromatography. Human HDL was isolated by subclass (HDL2b, 2a, 3a, 3b, 3c) from the plasma of healthy volunteers by sequential density gradient ultracentrifugation. HDL-apoA-I exchange (HAE) was measured by electron paramagnetic resonance (EPR) and non-denaturing gradient gel electrophoresis (NDGGE) following incubation with either spin-labeled or fluorescently-labeled, lipid-free apoA-I. Size-dependent effects were observed with rHDL particles, with the largest rHDL particles exhibiting 3-fold higher HAE compared to the smallest particles. In contrast, the HAE of human-derived pHDL particles was relatively constant across all subclasses at constant apoA-I concentration. Conclusions: HDL-apoA-I exchange is size-dependent in rHDL, with HAE positively associated with rHDL particle size, but it is size-independent in human pHDL. Our findings suggest that additional factors such as remodeling enzymes may facilitate apoA-I exchange from human pHDL.

Cholesterol efflux regulatory protein, Tangier disease and familial high-density lipoprotein deficiency

2000 ◽  
Vol 11 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Michael R. Hayden ◽  
Susanne M. Clee ◽  
Angela Brooks-Wilson ◽  
Jacques Genest ◽  
Alan Attie ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Regulatory Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
Tangier Disease

scholarly journals Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux

2020 ◽  
pp. jlr.RA120000920
Author(s):  
Oktawia Nilsson ◽  
Mikaela Lindvall ◽  
Laura Obici ◽  
Simon Ekström ◽  
Jens O Lagerstedt ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Peripheral Tissues ◽  
Structure Dynamics ◽  
Apolipoprotein A

Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of patients carrying either L75P or L174S ApoA-I amyloidogenic variants a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.

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