scholarly journals LDL-lipids from patients with hypercholesterolaemia and Alzheimer's disease are inflammatory to microvascular endothelial cells: mitigation by statin intervention

2015 ◽  
Vol 129 (12) ◽  
pp. 1195-1206 ◽  
Author(s):  
H.K. Irundika Dias ◽  
Caroline L.R. Brown ◽  
M. Cristina Polidori ◽  
Gregory Y.H. Lip ◽  
Helen R. Griffiths
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Microvascular Endothelial Cells ◽  
Low Density ◽  
High Cholesterol ◽  
Inflammatory Damage

We have established a novel anti-inflammatory and antioxidant role of statins towards oxidized fats in the “bad” cholesterol low density lipoprotein (LDL) particle from the blood of mid-life adults with high cholesterol. Oxidized LDL-fat levels were also higher in the blood of patients with dementia and caused inflammatory damage to cells that line blood vessels.

scholarly journals Role of LOX-1 (Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1) as a Cardiovascular Risk Predictor

2020 ◽  
Author(s):  
Joaquim Barreto ◽  
Sotirios K. Karathanasis ◽  
Alan Remaley ◽  
Andrei C. Sposito
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Risk ◽  
Neutralizing Antibodies ◽  
Randomized Clinical Trials ◽  
Transmembrane Protein ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density

Atherosclerosis, the underlying cause of cardiovascular disease (CVD), is a worldwide cause of morbidity and mortality. Reducing ApoB-containing lipoproteins—chiefly, LDL (low-density lipoprotein)—has been the main strategy for reducing CVD risk. Although supported by large randomized clinical trials, the persistence of residual cardiovascular risk after effective LDL reduction has sparked an intense search for other novel CVD biomarkers and therapeutic targets. Recently, Lox-1 (lectin-type oxidized LDL receptor 1), an innate immune scavenger receptor, has emerged as a promising target for early diagnosis and CV risk prediction and is also being considered as a treatment target. Lox-1 was first described as a 50 kDa transmembrane protein in endothelial cells responsible for oxLDL (oxidized LDL) recognition, triggering downstream pathways that intensify atherosclerosis via endothelial dysfunction, oxLDL uptake, and apoptosis. Lox-1 is also expressed in platelets, where it enhances platelet activation, adhesion to endothelial cells, and ADP-mediated aggregation, thereby favoring thrombus formation. Lox-1 was also identified in cardiomyocytes, where it was implicated in the development of cardiac fibrosis and myocyte apoptosis, the main determinants of cardiac recovery following an ischemic insult. Together, these findings have revealed that Lox-1 is implicated in all the main steps of atherosclerosis and has encouraged the development of immunoassays for measurement of sLox-1 (serum levels of soluble Lox-1) to be used as a potential CVD biomarker. Finally, the recent development of synthetic Lox-1 inhibitors and neutralizing antibodies with promising results in animal models has made Lox-1 a target for drug development. In this review, we discuss the main findings regarding the role of Lox-1 in the development, diagnosis, and therapeutic strategies for CVD prevention and treatment.

Protective Effects of Berberine against Low-Density Lipoprotein (LDL) Oxidation and Oxidized LDL-Induced Cytotoxicity on Endothelial Cells

2007 ◽  
Vol 55 (25) ◽  
pp. 10437-10445 ◽  
Author(s):  
Yih-Shou Hsieh ◽  
Wu-Hsien Kuo ◽  
Ta-Wei Lin ◽  
Horng-Rong Chang ◽  
Teseng-His Lin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density ◽  
Protective Effects

Hydrogen sulfide destroys lipid hydroperoxides in oxidized LDL

2009 ◽  
Vol 420 (2) ◽  
pp. 277-281 ◽  
Author(s):  
Markus K. Muellner ◽  
Sabine M. Schreier ◽  
Hilde Laggner ◽  
Marcela Hermann ◽  
Harald Esterbauer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hplc Analysis ◽  
Octadecadienoic Acid ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Hydroperoxides ◽  
Low Density ◽  
The Third ◽  
Haem Oxygenase

LOOHs (lipid hydroperoxides) in oxLDL [oxidized LDL (low-density lipoprotein)] are potentially atherogenic compounds. Recently, H2S was identified as the third endogenous gasotransmitter in the vasculature. H2O2 is known to be destroyed by H2S. Assuming that H2S may also react with LOOHs, the results show that H2S can destroy LOOHs in oxLDL. The ability of LOOH-enriched LDL to induce HO-1 (haem oxygenase 1) in endothelial cells was abolished by H2S pretreatment. HPLC analysis showed that 9-HPODE [(9S)-hydroperoxy-(10E,12Z)-octadecadienoic acid], a compound found in oxLDL, was reduced to 9-HODE [(9S)-hydroxy-(10E,12Z)-octadecadienoic acid] in the presence of H2S. Thus H2S may act as an antiatherogenic agent by reducing LOOHs to the less reactive LOHs and could abrogate the pathobiological activity of oxLDL.

Low density lipoprotein increases amyloid precursor protein processing to amyloidogenic pathway in differentiated SH-SY5Y cells

Biologia ◽  
2017 ◽  
Vol 72 (2) ◽  
Author(s):  
Panit Yamchuen ◽  
Rattima Jeenapongsa ◽  
Sutisa Nudmamud-Thanoi ◽  
Nanteetip Limpeanchob
Keyword(s):  
Amyloid Precursor Protein ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Neuroblastoma Cells ◽  
Density Lipoprotein ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Processing ◽  
Low Density ◽  
App Processing

AbstractHypercholesterolemia has been considered as a risk factor for Alzheimer’s disease (AD). In addition to low density lipoprotein (LDL), oxidized LDL plays some roles in AD pathology. Neurodegenerative effect of oxidized LDL was supported by the increased oxidative stress in neurons. To further investigate the role of oxidized LDL, the present study aimed to test its effect on amyloid precursor protein (APP) processing. The release of soluble APP (sAPP) was evaluated in differentiated SH-SY5Y neuroblastoma cells exposed to native (non-oxidized) or oxidized human LDL including mildly and fully oxidized LDL (mox- and fox-LDL). Non-amyloidogenic and amyloidogenic pathways were investigated using specific antibody against sAPP

scholarly journals Identification and isolation of endothelial cells based on their increased uptake of acetylated-low density lipoprotein.

1984 ◽  
Vol 99 (6) ◽  
pp. 2034-2040 ◽  
Author(s):  
J C Voyta ◽  
D P Via ◽  
C E Butterfield ◽  
B R Zetter
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Muscle Cells ◽  
Microvascular Endothelial Cells ◽  
Low Density ◽  
Fluorescent Intensity ◽  
Microvascular Endothelial

Acetylated-low density lipoprotein (Ac-LDL) is taken up by macrophages and endothelial cells via the "scavenger cell pathway" of LDL metabolism. In this report, aortic and microvascular endothelial cells internalized and degraded 7-15 times more [125I]-Ac-LDL than did smooth muscle cells or pericytes. Bound [125I]-Ac-LDL was displaced by unlabeled Ac-LDL, but not unmodified LDL. The ability to identify endothelial cells based on their increased metabolism of Ac-LDL was examined using Ac-LDL labeled with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (Dil-Ac-LDL). When cells were incubated with 10 micrograms/ml Dil-Ac-LDL for 4 h at 37 degrees C and subsequently examined by fluorescence microscopy, capillary and aortic endothelial cells were brilliantly fluorescent whereas the fluorescent intensity of retinal pericytes and smooth muscle cells was only slightly above background levels. Dil-Ac-LDL at the concentration used for labeling cells had no effect on endothelial cell growth rate. When primary cultures of bovine adrenal capillary cells were labeled with 10 micrograms/ml of Dil-Ac-LDL for 4 h at 37 degrees C, then trypsinized and subjected to fluorescence-activated cell sorting, pure cultures of capillary endothelial cells could be obtained. Utilizing this method, large numbers of early passage microvascular endothelial cells can be obtained in significantly less time than with conventional methods.

scholarly journals Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function

2005 ◽  
Vol 35 (3) ◽  
pp. 531-545 ◽  
Author(s):  
B Löhrke ◽  
T Viergutz ◽  
B Krüger
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Steroidogenic Enzymes ◽  
Cox 2

The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5–11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3β-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17β-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge.

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