Alteration of high-density lipoprotein functionality in Alzheimer’s disease patients

2017 ◽  
Vol 95 (8) ◽  
pp. 894-903 ◽  
Author(s):  
Paméla Camponova ◽  
Aurélie Le Page ◽  
Hicham Berrougui ◽  
Julie Lamoureux ◽  
Graham Pawelec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Density Lipoprotein ◽  
Healthy Subjects ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Elderly Subjects ◽  
The Difference

The aims of the present study were to determine whether high-density lipoprotein (HDL) functionality-mediated cholesterol efflux is altered in Alzheimer’s disease and to investigate the role and effect of amyloid-beta (Aβ) in the regulation of the anti-atherogenic activity of HDL. Eighty-seven elderly subjects were recruited, of whom 27 were healthy, 27 had mild cognitive impairment (MCI), and 33 had mild Alzheimer’s disease (mAD). Our results showed that total cholesterol levels are negatively correlated with the Mini-Mental State Examination (MMSE) score (r = –0.2602, p = 0.0182). HDL from the mAD patients was less efficient at mediating cholesterol efflux from J774 macrophages (p < 0.05) than HDL from the healthy subjects and MCI patients. While HDL from the MCI patients was also less efficient at mediating cholesterol efflux than HDL from the healthy subjects, the difference was not significant. Interestingly, the difference between the healthy subjects and the MCI and mAD patients with respect to the capacity of HDL to mediate cholesterol efflux disappeared when ATP-binding cassette transporter A1 (ABCA1)-enriched J774 macrophages were used. HDL fluidity was significantly inversely correlated with the MMSE scores (r = –0.4137, p < 0.009). In vitro measurements of cholesterol efflux using J774 macrophages showed that neither Aβ1-40nor Aβ1-42stimulate cholesterol efflux from unenriched J774 macrophages in basal or ABCA1-enriched J774 macrophages.

scholarly journals An Increased Plasma Level of ApoCIII-Rich Electronegative High-Density Lipoprotein May Contribute to Cognitive Impairment in Alzheimer’s Disease

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 542
Author(s):  
Hua-Chen Chan ◽  
Liang-Yin Ke ◽  
Hsiao-Ting Lu ◽  
Shih-Feng Weng ◽  
Hsiu-Chuan Chan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Liquid Chromatography ◽  
Cognitive Impairment ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Efflux Capacity ◽  
Tnf Α

High-density lipoprotein (HDL) plays a vital role in lipid metabolism and anti-inflammatory activities; a dysfunctional HDL impairs cholesterol efflux pathways. To understand HDL’s role in patients with Alzheimer’s disease (AD), we analyzed the chemical properties and function. HDL from AD patients (AD-HDL) was separated into five subfractions, H1–H5, using fast-protein liquid chromatography equipped with an anion-exchange column. Subfraction H5, defined as the most electronegative HDL, was increased 5.5-fold in AD-HDL (23.48 ± 17.83%) in comparison with the control HDL (4.24 ± 3.22%). By liquid chromatography mass spectrometry (LC/MSE), AD-HDL showed that the level of apolipoprotein (apo)CIII was elevated but sphingosine-1-phosphate (S1P)-associated apoM and anti-oxidative paraoxonase 1 (PON1) were reduced. AD-HDL showed a lower cholesterol efflux capacity that was associated with the post-translational oxidation of apoAI. Exposure of murine macrophage cell line, RAW 264.7, to AD-HDL induced a vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts alongside a concomitant increase of tumor necrosis factor-α (TNF-α) detectable in the cultured medium. In conclusion, AD-HDL had a higher proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated increase in pro-inflammatory (apoCIII, TNF-α) components might favor Amyloid β assembly and neural inflammation. A compromised cholesterol efflux capacity of AD-HDL may also contribute to cognitive impairment.

Oxidized plasma high-density lipoprotein is decreased in Alzheimer's disease

2006 ◽  
Vol 41 (10) ◽  
pp. 1542-1547 ◽  
Author(s):  
Constanze Bergt ◽  
Takanari Nakano ◽  
Jochen Ditterich ◽  
Charles DeCarli ◽  
Jason P. Eiserich
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Plasma High Density Lipoprotein ◽  
Plasma High Density

Abstract 389: Covalent Modifications of Apolipoproteins in High Density Lipoprotein by Oxidized Phospholipids Impair the Cholesterol Efflux Function of High Density Lipoprotein and are Detected in Hyperlipidemic Plasma

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Detao Gao ◽  
Lifang Zhang ◽  
Eugene Podrez
Keyword(s):  
High Density Lipoprotein ◽  
Human Plasma ◽  
Protein Function ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Oxidized Phospholipids ◽  
Protein Adduction ◽  
Covalent Modifications

Oxidized phospholipids (oxPLs) accumulate at sites of oxidative stress and contribute significantly to atherosclerosis and thrombosis. Most oxPLs have electrophilic substituents and are highly likely to form covalent adducts with proteins, thus compromising protein function. Detection of covalent interactions between oxPLs and proteins could provide important information regarding the type of proteins preferentially modified by oxPLs. However, to date, such studies are extremely limited due to significant technical challenges. We now carry out systematic studies on the protein adduction by oxPLs formed in murine and human plasma. Plasma samples were exposed to a physiologically relevant myeloperoxidase/H 2 O 2 /NO 2 – oxidizing system of phagocytes. Protein adduction by the oxPLs generated in plasma was assessed using LC-MS/MS after tryptic digestion and peptide enrichment using a novel method that we developed. We found that HDL apolipoproteins are the major targets of modification by oxPLs in both murine and human plasma. For apoA-I, the most abundant apolipoprotein in HDL, the major modification sites of oxPLs were located in the region (AA144-186), which is critical for the ABCA1 mediated cholesterol efflux to HDL. We further demonstrated that human apoA-I was also heavily crosslinked by specific oxPLs via histidine and lysine residues located in the region (AA144-186) with apoA-I, or other apolipoproteins, including apoA-II, apoA-IV and apoC-I. In vitro experiments demonstrated that oxPLs modification on lipid free apoA-I or nascent HDL (HDL3) dramatically impairs their function as cholesterol efflux mediators. Using hyperlipidemic LDLr-/- mice, we detected a crosslink adduct of apoA-II with apoE by oxPL in murine plasma. To the best of our knowledge, this is the first report for the detection of endogenous protein adducts with oxPLs.

scholarly journals High-density lipoprotein 3 physicochemical modifications induced by interaction with human polymorphonuclear leucocytes affect their ability to remove cholesterol from cells

1996 ◽  
Vol 314 (1) ◽  
pp. 285-292 ◽  
Author(s):  
Anne COGNY ◽  
Véronique ATGER ◽  
Jean-Louis PAUL ◽  
Théophile SONI ◽  
Nicole MOATTI
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
High Density ◽  
Molar Ratio ◽  
Polymorphonuclear Leucocytes ◽  
Partial Loss ◽  
Apo Ai

1. We have recently reported that a short incubation (60 min) in vitro of high-density lipoprotein (HDL) 3 with human polymorphonuclear leucocytes (PMNs) leads to a proteolytic cleavage of apolipoprotein (apo) AII and to a change in the distribution of apo AI isoforms [Cogny, Paul, Atger, Soni and Moatti (1994) Eur. J. Biochem. 222, 965–973]. Since PMNs have been observed to be present in the earliest atherosclerotic lesions for a number of days, we investigated the HDL3 physicochemical modifications induced by in vitro interaction for a long period of time (24 h) with PMNs and the consequences of the changes on the ability of HDL3 to remove cholesterol from cells. 2. The stimulated PMN modification of HDL3 over 24 h resulted in a partial loss of protein with no variation in lipid molar ratio and a loss of 50% of HDL α-tocopherol content. The decrease in total protein was due first to a complete degradation of apo AII, and secondly to a partial loss of apo AI. The apo AI remaining on the particles was in part hydrolysed and the apo AI-1 isoform was completely shifted to the apo AI-2 isoform. These apo changes were accompanied by a displacement of the native HDL3 apparent size toward predominantly larger particles. 3. The ability of PMN-modified HDL3 to remove 3H-labelled free cholesterol from cells was measured in two cell lines: Fu5AH rat hepatoma cells and J774 mouse macrophages. HDL3 which had only a limited contact with PMNs (60 min) showed only a small non-significant reduction in the efficiency of cholesterol efflux. On the other hand, compared with native HDL3, HDL3 modified by PMNs for 24 h had a markedly reduced ability to remove cholesterol from cells, regardless of the type of cell. 4. The results suggest that PMN-modified HDL3, if occurring in vivo, could contribute to acceleration of the atherogenic process by decreasing the cholesterol efflux from cells.

scholarly journals ADAM17 Boosts Cholesterol Efflux and Downstream Effects of High-Density Lipoprotein on Inflammatory Pathways in Macrophages

2021 ◽  
Author(s):  
Vishal Kothari ◽  
Jingjing Tang ◽  
Yi He ◽  
Farah Kramer ◽  
Jenny E. Kanter ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Myeloid Cell ◽  
Peritoneal Macrophages ◽  
High Density ◽  
Cholesterol Depletion ◽  
Proinflammatory Responses ◽  
Anti Inflammatory

Objective: HDL (high-density lipoprotein) can exert both anti-inflammatory and proinflammatory effects in macrophages due to its ability to induce cholesterol depletion. Because cholesterol depletion also increases sheddase activity of the membrane protease ADAM17 (ADAM metallopeptidase domain 17) in other cells, we examined if ADAM17 plays a role in HDL’s effects on inflammatory processes in macrophages in vitro and in vivo. Approach and Results: Sorted peritoneal macrophages from human APOA1 (apolipoprotein A1) transgenic LDL (low-density lipoprotein) receptor-deficient ( APOA1 Tg ; Ldlr −/− ) mice with and without myeloid cell-targeted ADAM17-deficiency were studied in parallel with wildtype and ADAM17-deficient bone marrow-derived macrophages stimulated with HDL in vitro. HDL increased ADAM17 expression and activity in macrophages. Furthermore, ADAM17-deficient macrophages exhibited reduced expression of ABCA1 (ATP-binding cassette A1) and reduced cholesterol efflux and were cholesterol loaded. This was caused by the absence of shedding of TNFα, a major ADAM17 substrate. Sorted thioglycollate-elicited peritoneal macrophages freshly isolated from APOA1 Tg ; Ldlr −/− mice, which have higher HDL levels than Ldlr −/− controls, showed reduced expression of interferon-inducible genes in response to lipopolysaccharide or interferon-β, but exacerbated proinflammatory responses to lipopolysaccharide for Tnfa , Cxcl1 , Ccl2 , and Il1b , phenocopying cells stimulated with HDL in vitro. These effects were all prevented in ADAM17-deficient macrophages and associated with lower concentrations of large HDL particles in APOA1 Tg ; Ldlr −/− mice with myeloid cell-targeted ADAM17-deficiency. Conclusions: The increased cholesterol loading of ADAM17-deficient macrophages prevents both anti-inflammatory and proinflammatory responses of HDL. Our findings demonstrate a novel role for ADAM17 in maintaining cholesterol efflux in macrophages, thereby regulating the immune functions of these cells.

Sign in / Sign up

Export Citation Format

Share Document