scholarly journals Changes in High-Density Lipoproteins Related to Outcomes in Patients with Acute Stroke

2020 ◽  
Vol 9 (7) ◽  
pp. 2269
Author(s):  
Lourdes M. Varela ◽  
Elena Meseguer ◽  
Bertrand Lapergue ◽  
David Couret ◽  
Pierre Amarenco ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Density Lipoprotein ◽  
Intravenous Thrombolysis ◽  
High Density ◽  
Paraoxonase 1 ◽  
Intercellular Adhesion Molecule ◽  
High Density Lipoproteins ◽  
Stroke Patients ◽  
Lipoprotein Subfractions ◽  
Anti Inflammatory

Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 months. Plasma samples were obtained from stroke patients treated with intravenous thrombolysis. Levels of cardiovascular and inflammatory markers in plasma were measured using the Human CVD Panel 1 (Milliplex® MAP). Lipoprotein subfractions from plasma were quantified by non-denaturing acrylamide gel electrophoresis, using the Lipoprint®-System (Quantimetrix®), and HDLs were isolated by ultracentrifugation. Relative amounts of paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT) in the isolated HDLs were determined by Western blot. HDL anti-inflammatory function was evaluated in human blood–brain barrier endothelial cells stimulated with 100 ng/mL TNFα, and HDL antioxidant function was evaluated via their capacity to limit copper-induced low-density lipoprotein oxidation. Stroke patients with unfavorable outcomes had a lower proportion of small-sized HDLs and increased plasma levels of E-selectin (SELE) and the intercellular adhesion molecule 1 (ICAM1). HDLs from patients with unfavorable outcomes had lower levels of PON1 and displayed a blunted capacity to reduce the expression of SELE, interleukin 8 (IL8) and the monocyte chemoattractant protein-1 (MCP1) mRNA induced by TNFα in endothelial cells. These HDLs also had a reduced antioxidant capacity relative to HDLs from healthy donors. In conclusion, an increased ratio of large/small HDLs with impaired anti-inflammatory and antioxidant capacities was associated with unfavorable outcomes in stroke patients. Alteration of HDL functionality was mainly associated with a low amount of PON1 and high amount of AAT.

Abstract 260: Knockout of Apolipoprotein A-II Has Dramatic Effects on High-Density Lipoprotein Subspecies Distribution

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Scott M Gordon ◽  
Catherine A Reardon ◽  
Godfrey S Getz ◽  
W S Davidson
Keyword(s):  
Gel Filtration ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Ionization Mass ◽  
Associated Proteins ◽  
Compositional Diversity ◽  
The Impact ◽  
Modest Effect

High density lipoproteins (HDL) are a highly heterogeneous population of particles composed of various lipids and proteins. They have been demonstrated to possess a diverse variety of functional properties which are thought to contribute to protection against cardiovascular disease (CVD). Proteomics studies have identified up to 75 different proteins which can associate with HDL. The basis for the compositional diversity of HDL is not known but a better understanding will yield important information about its broad functional diversity. To investigate the impact of common HDL apolipoproteins on the distribution of other apolipoproteins, we have begun to systematically fractionate plasma from various HDL apolipoprotein KO mice. Plasma from apoA-I, apoA-IV and apoA-II global KO mice was applied to gel filtration chromatography to distinguish HDL size populations. HDL particles sequestered by a phospholipid binding resin were proteomically analyzed by electrospray ionization mass spectrometry. By comparing elution volume shifts (i.e. particle size variations) for each HDL protein between WT controls and the KO models, we assessed the impact of the deleted protein on HDL size distributions. Ablation of apoA-I, while decreasing total HDL phospholipid by 70%, had a surprisingly small impact on the distribution of the majority of other HDL associated proteins - affecting only 9 of them. Genetic apoA-IV ablation had a similar modest effect shifting a distinct subset of 9 proteins. However, loss of apoA-II, in addition to causing a similar 70% reduction in overall HDL phospholipids, affected the size distribution of some 45 HDL proteins (including several complement proteins and paraoxonase-1). These data suggest that apoA-I, while associated with the majority of HDL phospholipid, may actually interact with relatively few of the lower abundance proteins known to be associated with HDL. ApoA-II on the other hand, may interact with many of these, perhaps acting as a docking site or adaptor molecule.

Plasma-derived and synthetic high-density lipoprotein inhibit tissue factor in endothelial cells and monocytes

2016 ◽  
Vol 473 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Alice Ossoli ◽  
Alan T. Remaley ◽  
Boris Vaisman ◽  
Laura Calabresi ◽  
Monica Gomaraschi
Keyword(s):  
Endothelial Cells ◽  
High Density Lipoprotein ◽  
Tissue Factor ◽  
Density Lipoprotein ◽  
High Density ◽  
Coagulation Cascade ◽  
High Density Lipoproteins

Atheroprotection mediated by high-density lipoproteins could also be related to their ability to inhibit the expression of tissue factor, the main activator of the coagulation cascade, in endothelial cells and in monocytes.

Dysfunctional high-density lipoprotein: the role of myeloperoxidase and paraoxonase-1

2020 ◽  
Vol 27 ◽  
Author(s):  
Tiziana Bacchetti ◽  
Gianna Ferretti ◽  
Federico Carbone ◽  
Stefano Ministrini ◽  
Fabrizio Montecucco ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Protective Factor ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Atherosclerotic Cardiovascular Disease ◽  
Potential Marker ◽  
And Function

: Low circulating high-density lipoproteins (HDL) are not only a defining criteria for metabolic syndrome, but are more generally associated with atherosclerotic cardiovascular disease (ASCVD) and other chronic diseases. Oxidative stress, a hallmark of cardio-metabolic disease, further influences HDL activity by suppressing their function. Especially the leukocyte-derived enzyme myeloperoxidase (MPO) has recently attracted great interest as it catalyzes the formation of oxidizing reactive species that modify the structure and function of HDL, ultimately increasing cardiovascular risk. Contrariwise, paraoxonase-1 (PON1) is an HDL-associated enzyme that protects HDL from lipid oxidation, and then acts as a protective factor against ASCVD. Noteworthy, recent studies have demonstrated how MPO, PON1 and HDL form a functional complex in which PON1 partially inhibits the MPO activity, while MPO in turn partially inactivates PON1.In line with that, high MPO/PON1 ratio characterizes patients with ASCVD and metabolic syndrome and has been suggested as a potential marker of dysfunctional HDL as well as a predictor of ASCVD. In this review, we summarize the evidence on the interactions between MPO and PON1 with regard to their structure, function and interaction with HDL activity. We also provide an overview on in vitro and experimental animal models, finally focusing on clinical evidence from cohort of patients with ASCVD and metabolic syndrome.

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.

scholarly journals High density lipoprotein subfractions and paraoxonase 1 in children

2016 ◽  
Vol 63 (3) ◽  
Author(s):  
Jana Muchová ◽  
Lucia Andrezálová ◽  
Stanislav Oravec,Zuzana Nagyová ◽  
Iveta Garaiova ◽  
Zdeňka Ďuračková
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Study Groups ◽  
High Density ◽  
Paraoxonase 1 ◽  
Low Density ◽  
Lipoprotein Subfractions ◽  
Hdl Subfractions ◽  
Ldl Subfractions

The Lipoprint system (Quantimetrix Corp., CA, USA), enables the determination of 10 high density lipoprotein (HDL) subfractions in contrast to the 5 HDL subfractions that can be determined by ultracentrifuge analysis. HDL subfractions, and their relationships to the arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1), together with total-, very low density lipoprotein- and low density lipoprotein (LDL)-cholesterol and LDL subfractions were investigated in the serum of 27 mildly hypercholesterolemic children and 21 healthy controls. Our results suggest the antiatherogenity of large HDL (L-HDL) subfractions and the atherogenity of small HDL (S-HDL) subfractions in the study groups. However, the relationship between the intermediate HDL (I-HDL) subfractions with the LDL subfractions and other lipoproteins did not suggest that I-HDL subfractions are antiatherogenic. No significant association between PON1-A and the HDL subfractions was found. In contrast, PON1-L activity positively correlated with the antiatherogenic large HDL1 subfraction and negatively with intermediate HDL subfractions 4, 5 and 6. Our results contribute to the knowledge of the roles of total HDL and ten individual HDL subfractions in children and adolescents.

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