scholarly journals High-density lipoprotein remodelled in hypercholesterolaemic blood induce epigenetically driven down-regulation of endothelial HIF-1α expression in a preclinical animal model

2019 ◽  
Vol 116 (7) ◽  
pp. 1288-1299 ◽  
Author(s):  
Soumaya Ben-Aicha ◽  
Rafael Escate ◽  
Laura Casaní ◽  
Teresa Padró ◽  
Esther Peña ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Down Regulation ◽  
Cholesterol Levels ◽  
In Vivo Effects ◽  
Mirna Content

Abstract Aims High-density lipoproteins (HDLs) are circulating micelles that transport proteins, lipids, and miRNAs. HDL-transported miRNAs (HDL-miRNAs) have lately received attention but their effects on vascular cells are not fully understood. Additionally, whether cardiovascular risk factors affect HDL-miRNAs levels and miRNA transfer to recipient cells remains equally poorly known. Here, we have investigated the changes induced by hypercholesterolaemia on HDL-miRNA levels and its effect on recipient endothelial cells (ECs). Methods and results Pigs were kept on a high-fat diet (HC; n = 10) or a normocholesterolaemic chow (NC; n = 10) for 10 days reaching cholesterol levels of 321.0 (229.7–378.5) mg/dL and 74.0 (62.5–80.2) mg/dL, respectively. HDL particles were isolated, purified, and quantified. HDL-miRNA profiling (n = 149 miRNAs) of HC- and NC-HDLs was performed by multipanel qPCR. Cell cultures of porcine aortic ECs were used to determine whether HDL-miRNAs were delivered to ECs. Potential target genes modulated by miRNAs were identified by bioinformatics and candidate miRNAs were validated by molecular analysis. In vivo effects in the coronary arteries of normocholesterolaemic swine administered HC- or NC-HDLs were analysed. Among the HDL-miRNAs, four were found in different amounts in HC- and NC-HDL (P < 0.05). miR-126-5p and -3p and miR-30b-5p (2.7×, 1.7×, and 1.3×, respectively) were found in higher levels and miR-103a-3p and miR-let-7g-5p (−1.6×, −1.4×, respectively) in lower levels in HC-HDL. miR-126-5p and -3p were transferred from HC-HDL to EC (2.5×; P < 0.05), but not from NC-HDL, by a SRB1-mediated mechanism. Bioinformatics revealed that HIF1α was the miR-126 target gene with the highest predictive value, which was accordingly found to be markedly reduced in HC-HDL-treated ECs and in miR126 mimic transfected ECs. In vivo validation confirmed that HIF1α was diminished in the coronary endothelial layer of NC pigs administered HC-HDL vs. those administered NC-HDL (P < 0.05). Conclusion Hypercholesterolaemia induces changes in the miRNA content of HDL enhancing miR126 and its delivery to ECs with the consequent down-regulation of its target gene HIF1α.

scholarly journals Evidence for the role of high density lipoproteins in mediating the antioxidant effect of estrogens

2000 ◽  
pp. 79-83 ◽  
Author(s):  
W Abplanalp ◽  
MD Scheiber ◽  
K Moon ◽  
B Kessel ◽  
JH Liu ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Antioxidant Effect ◽  
High Density ◽  
In Vivo Studies ◽  
Ldl Oxidation ◽  
High Density Lipoproteins ◽  
Oh Groups

Estrogens possess strong antioxidant effects in vitro, but in vivo studies in humans have yielded conflicting results. Little is known regarding factors that mediate the antioxidant effect of estrogens in vivo. In this study the potential role of high density lipoprotein (HDL) was examined. The antioxidant effect of estradiol-17beta (E2) added to low density lipoprotein (LDL) was lost after dialysis. In contrast, the antioxidant effect of E2 added to HDL was conserved after dialysis, suggesting that E2 was bound to HDL. Binding of E2 to LDL increased after esterification (especially to long chain fatty acids). In the presence of HDL, an increased amount of E2 was transferred to LDL. E2-17 ester was as potent as E2 in preventing LDL oxidation in vitro, but 3,17-diesters were not as effective (E2=E2-17 ester>E2-3 ester>E2-3,17 diester). This was also supported by experiments which showed that estrogens with masked 3-OH groups were not effective as antioxidants. These studies provide evidence that HDL could facilitate the antioxidant effect of E2 through initial association, esterification and eventual transfer of E2 esters to LDL. Therefore it is critical that HDL peroxidation parameters be evaluated in subjects receiving estrogen replacement therapy.

scholarly journals The Content of Low Density Lipoprotein, High Density Lipoproteins, Cholesterol on Pen Shells (Atrina Pectinata) Fish Catch in Kenjeran Surabaya

2020 ◽  
Vol 7 (2) ◽  
pp. 51
Author(s):  
Rio Khalif Eldiaz ◽  
Agustono Agustono ◽  
Kustiawan Tri Pursetyo
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Digestive Organs ◽  
Cholesterol Levels ◽  
Fish Catch ◽  
Atrina Pectinata

Pen Shells (A. pectinata) Is one type of a clam that is mostly consumed, Cholesterol levels included in a category high. Although the high cholesterol levels. Shells also contain levels commonly called ldl cholesterol evil . Having shells also levels of hdl, Cholesterol levels total normal in plasma adults is of 120 until 200 mg/dl. Different from its function at the time of cholesterol levels normal, the higher cholesterol levels in the blood, the greater the risk of atherosclerosis also. The purpose of this research is to get information about ldl levels , hdl and cholesterol contained in shells kampak , as well as to determine the shells kampak who most worthy for consumption. Parameter that observed in this research was ldl , hdl , cholesterol .This study using methods descriptive against the difference levels of low density lipopprotein ( ldl ) and high-density lipoproteins ( hdl ) and cholesterol in any bivalve hatchets the results of catch fishermen in kenjeran surabaya. Average levels of ldl on pen shells (A. pictinata) In the meat is 30,990 mg/100g, in the muscle is 28,329 mg/100g and in the Digestive organs is 25,225 mg/100g ; The average levels of hdl on pen shells (A. pictinata) in the meat is 96,772 mg/100g, in the muscle is 87,139 mg/100g and in the Digestive organs is 67,516 mg/100g ; average levels of cholesterol on pen shells (A. pictinata) in the meat is 165,609 mg/100g, in the muscle is 147,382 mg/100g and in the Digestive organs is 114,551 mg/100g. Levels of LDL, HDL and cholesterol Lead to results same that is the most number are located on the meat, then muscle and at least there are on an disgestive organ.

Differential Effects of Reconstituted High-density Lipoprotein on Coagulation, Fibrinolysis and Platelet Activation during Human Endotoxemia

1997 ◽  
Vol 77 (02) ◽  
pp. 303-307 ◽  
Author(s):  
Dasja Pajkrt ◽  
Peter G Lerch ◽  
Tom van der Poll ◽  
Marcel Levi ◽  
Marlies Illi ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Plasma Levels ◽  
Density Lipoprotein ◽  
High Density ◽  
Tissue Type ◽  
High Density Lipoproteins ◽  
Double Blind

SummaryHigh-density lipoproteins (HDL) can bind and neutralize lipopoly- saccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1+2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachido- nate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia.

scholarly journals Transfer and Enzyme-Mediated Metabolism of Oxidized Phosphatidylcholine and Lysophosphatidylcholine between Low- and High-Density Lipoproteins

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1045
Author(s):  
Naoko Sawada ◽  
Takashi Obama ◽  
Mirei Mizuno ◽  
Kiyoshi Fukuhara ◽  
Sanju Iwamoto ◽  
...  
Keyword(s):  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
High Density ◽  
Short Chain ◽  
High Density Lipoproteins ◽  
Dependent Manner ◽  
Atheromatous Plaques ◽  
Oxidized Phosphatidylcholine

Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL), known as risk factors for cardiovascular disease, have been observed in plasma and atheromatous plaques. In a previous study, the content of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) species stayed constant in isolated in vivo oxLDL but increased in copper-induced oxLDL in vitro. In this study, we prepared synthetic deuterium-labeled 1-palmitoyl lysoPC and palmitoyl-glutaroyl PC (PGPC), a short chain-oxPC to elucidate the metabolic fate of oxPC and lysoPC in oxLDL in the presence of HDL. When LDL preloaded with d13-lysoPC was mixed with HDL, d13-lysoPC was recovered in both the LDL and HDL fractions equally. d13-LysoPC decreased by 50% after 4 h of incubation, while d13-PC increased in both fractions. Diacyl-PC production was abolished by an inhibitor of lecithin-cholesterol acyltransferase (LCAT). When d13-PGPC-preloaded LDL was incubated with HDL, d13-PGPC was transferred to HDL in a dose-dependent manner when both LCAT and lipoprotein-associated phospholipase A2 (Lp-PLA2) were inhibited. Lp-PLA2 in both HDL and LDL was responsible for the hydrolysis of d13-PGPC. These results suggest that short chain-oxPC and lysoPC can transfer between lipoproteins quickly and can be enzymatically converted from oxPC to lysoPC and from lysoPC to diacyl-PC in the presence of HDL.

scholarly journals High-Density Lipoproteins and Serum Amyloid A (SAA)

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Nancy R. Webb
Keyword(s):  
Serum Amyloid A ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Density Lipoprotein ◽  
High Density ◽  
Serum Amyloid ◽  
High Density Lipoproteins ◽  
Amyloid A

Abstract Purpose of Review Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL. Recent Findings Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of inducing inflammatory responses in vitro and in vivo. Factors that modulate the equilibrium between lipid-free and HDL-associated SAA have been identified. Summary HDL may serve to limit SAA’s bioactivities in vivo. Understanding the factors leading to the release of systemic SAA from HDL may provide insights into chronic disease mechanisms.

scholarly journals The effects of insulin deficiency on the plasma clearance and exchange of high-density-lipoprotein phosphatidylcholine in rats

1992 ◽  
Vol 281 (3) ◽  
pp. 851-857 ◽  
Author(s):  
I J Martins ◽  
T G Redgrave
Keyword(s):  
Plasma Clearance ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Cholesteryl Oleate ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Phospholipid Transfer ◽  
Plasma High Density

Triolein/cholesteryl oleate/cholesterol/phosphatidylcholine emulsions designed to model the lipid composition of chylomicrons were injected intravenously into control and streptozotocin-treated insulin-deficient rats. As previously described for lymph chylomicrons, the emulsion triolein was hydrolysed and phosphatidylcholine was transferred to the plasma high-density lipoproteins (HDL). This mechanism was used to introduce a phospholipid label into HDL in vivo. The subsequent clearance of phospholipid radioactivity from the plasma of insulin-deficient rats was significantly slower than in controls (P less than 0.025). Plasma clearance was similarly slower in insulin-deficient rats after injection of HDL that was previously labelled with radioactive phospholipids. After injection, the phospholipid label redistributed rapidly between the large-particle fraction of plasma lipoproteins (very-low- and low-density lipoproteins), and the lighter and heavier fractions of HDL. Compared with control rats, in insulin-deficient rats less of the phospholipid label was distributed to the lighter HDL fraction and more to the heavier HDL fraction, and this difference was not due to changes in activity of lecithin: cholesterol acyltransferase or in the apparent activity of phospholipid transfer protein. In insulin-deficient rats the changes in HDL phospholipid clearance and exchange appeared to be secondary to the associated hypertriglyceridaemia and the related changes in distribution of phospholipids between classes of plasma lipoproteins.

Binding of thyroxine and 3,5,3'-triiodothyronine to trout plasma lipoproteins

1992 ◽  
Vol 262 (5) ◽  
pp. E712-E720 ◽  
Author(s):  
P. J. Babin
Keyword(s):  
Nutritional Status ◽  
Binding Sites ◽  
Density Lipoprotein ◽  
High Density ◽  
Plasma Lipoproteins ◽  
High Density Lipoproteins ◽  
Minor Role ◽  
Very Low Density Lipoproteins

The plasma vectors of thyroid hormones (TH) in trout have been characterized. Plasma components were separated by density gradient ultracentrifugation after first labeling binding sites with trace levels of radioactive hormones, both in vivo and in vitro. Lipoproteins play only a minor role in humans but are major carriers of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in trout plasma. More than 67% of T4 and 89% of T3 were bound to lipoproteins (density less than 1.210 g/ml), predominantly to high-density lipoproteins (HDL), regardless of the nutritional status of the animals. The percentage of hormone bound to very-low-density lipoproteins, on the other hand, was proportional to their concentration and thus to nutritional status. T3 and T4 could also bind to vitellogenin, a very-high-density lipoprotein, which could transfer TH to the yolk of oocytes. Homologous ligand displacement indicated that T3 could bind to at least two classes of saturable sites in the plasma. In addition, plasma HDL were the major binding sites with low affinity (1.7 +/- 0.4 x 10(5) M-1) but with high capacity (3.1 +/- 0.3 x 10(-5) M). In conclusion, these results show that lipoproteins are the principal binding sites of TH in trout plasma.

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