scholarly journals Vasoprotective Functions of High-Density Lipoproteins Relevant to Alzheimer’s Disease Are Partially Conserved in Apolipoprotein B-Depleted Plasma

2019 ◽  
Vol 20 (3) ◽  
pp. 462 ◽  
Author(s):  
Emily Button ◽  
Megan Gilmour ◽  
Harleen Cheema ◽  
Emma Martin ◽  
Andrew Agbay ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Vascular Inflammation ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Healthy Humans ◽  
Polyethylene Glycol Precipitation ◽  
Endothelial Nitric Oxide

High-density lipoproteins (HDL) are known to have vasoprotective functions in peripheral arteries and many of these functions extend to brain-derived endothelial cells. Importantly, several novel brain-relevant HDL functions have been discovered using brain endothelial cells and in 3D bioengineered human arteries. The cerebrovascular benefits of HDL in healthy humans may partly explain epidemiological evidence suggesting a protective association of circulating HDL levels against Alzheimer’s Disease (AD) risk. As several methods exist to prepare HDL from plasma, here we compared cerebrovascular functions relevant to AD using HDL isolated by density gradient ultracentrifugation relative to apoB-depleted plasma prepared by polyethylene-glycol precipitation, a common high-throughput method to evaluate HDL cholesterol efflux capacity in clinical biospecimens. We found that apoB-depleted plasma was functionally equivalent to HDL isolated by ultracentrifugation in terms of its ability to reduce vascular Aβ accumulation, suppress TNFα-induced vascular inflammation and delay Aβ fibrillization. However, only HDL isolated by ultracentrifugation was able to suppress Aβ-induced vascular inflammation, improve Aβ clearance, and induce endothelial nitric oxide production.

scholarly journals The Role of High-Density Lipoproteins in Reducing the Risk of Vascular Diseases, Neurogenerative Disorders, and Cancer

Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Donovan McGrowder ◽  
Cliff Riley ◽  
Errol Y. St. A. Morrison ◽  
Lorenzo Gordon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Protective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory

High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including “healthy” diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.

Abstract 574: High-Density Lipoproteins Suppress Amyloid Beta Induced Human Brain Microvascular Endothelial Cell Activation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Emily B Button ◽  
Jerome Robert ◽  
Sophie K Stukus ◽  
Guilaine Boyce ◽  
Ebrima Gibbs ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Amyloid Beta ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Levels ◽  
Microvascular Endothelial

Introduction: Epidemiological studies suggest a link between plasma high-density lipoprotein (HDL) cholesterol levels and Alzheimer’s disease (AD) risk through mechanisms that are not understood. We hypothesize that HDL protects against AD through actions at the blood-brain-barrier. HDL has vasoprotective functions in large peripheral arteries, however, it is unknown if these functions extend to cerebral vessels to reduce the contribution of cerebrovascular dysfunction in AD pathogenesis. We investigated in vitro interactions between HDL and amyloid beta (Aβ), the toxic peptide known to accumulate in AD, in peripheral and brain-derived endothelial cells (EC). Methods: HDL was isolated by density gradient ultracentrifugation and added to human umbilical vein endothelial cells (HUVEC) or human cerebral microvascular endothelial cells (hCMEC/D3). Cell activation was measured by counting adhered labelled peripheral blood mononuclear cells (PBMC) after stimulation with tumour necrosis factor α (TNFα) or Aβ. Aβ binding and uptake into cells was measured using ELISA and immunofluorescence. All experiments included at least 4 independent replicates. Results: We demonstrate that HDL attenuates Aβ-induced EC activation independent of nitric oxide production, miR-233 and changes in adhesion molecule expression. Rather, HDL acts through scavenger receptor BI to block Aβ uptake into ECs and, in vitro , can maintain Aβ in a soluble state. We validated our results using three dimensional engineered vessels composed of primary human endothelial and smooth muscle cells. Following Aβ addition to the abluminal (brain) side, we demonstrated that HDL circulated within the lumen attenuates EC activation, again independent of intracellular adhesion molecule changes. Conclusions: We show that the anti-inflammatory activities of HDL extend to cerebrovascular endothelial cells and work to suppress Aβ-induced activation through a novel mechanism involving the inhibition of Aβ binding and uptake into cells through SR-BI. The protective role for HDL against Aβ may explain the epidemiological evidence supporting a protective effect of high plasma HDL cholesterol levels against dementia.

scholarly journals High-Density Lipoproteins and Cerebrovascular Integrity in Alzheimer’s Disease

2014 ◽  
Vol 19 (4) ◽  
pp. 574-591 ◽  
Author(s):  
Sophie Stukas ◽  
Jérôme Robert ◽  
Cheryl L. Wellington
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Density ◽  
High Density Lipoproteins

scholarly journals High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Josefien W. Hommes ◽  
Rachel M. Kratofil ◽  
Sigrid Wahlen ◽  
Carla J. C. de Haas ◽  
Reeni B. Hildebrand ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Bloodstream Infections ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Dependent Manner ◽  
Biological Functions ◽  
Healthy Humans

AbstractStaphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT−/− mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT−/− mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus.

scholarly journals High-Density Lipoproteins and the Kidney

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Arianna Strazzella ◽  
Alice Ossoli ◽  
Laura Calabresi
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Lcat Deficiency ◽  
Progression Of Renal Disease ◽  
The Impact

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.

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