scholarly journals Association of PCSK9 with human plasma Lipoproteins

2021 ◽  
pp. 7-13
Author(s):  
Aikaterini N. Tsouka ◽  
Alexandros D. Tselepis
Keyword(s):  
Human Plasma ◽  
Plasma Levels ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Main Function ◽  
Pathophysiological Role ◽  
Density Lipoprotein Receptor ◽  
Ldl Uptake

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is a serine protease primarily expressed in the liver. The main function of circulating PCSK9 relates to its binding to the low-density lipoprotein receptor (LDL-R) in hepatocytes, increasing its endosomal and lysosomal degradation. This results in the inhibition of LDL-R recycling to the cell surface and therefore in the reduction of the hepatic LDL uptake, leading to the increase in plasma levels of LDL-cholesterol. Several studies have demonstrated that the plasma levels of PCSK9 are correlated with those of the ApoB-containing lipoproteins; LDL, Lp(a) and Triglyceride-Rich Lipoproteins (TRL). Furthermore, it has been shown that PCSK9 binds to the LDL and Lp(a) particles and significantly influences TRL metabolism. By contrast, controversial results exist concerning the association of PCSK9 with High Density Lipoprotein (HDL). In the present review we present existing data on the association of PCSK9 with human plasma lipoprotein particles and its possible pathophysiological role.

Studies on the Thromboplastic Effect of Human Plasma Lipoproteins

1976 ◽  
Vol 35 (01) ◽  
pp. 178-185 ◽  
Author(s):  
Helena Sandberg ◽  
Lars-Olov Andersson
Keyword(s):  
High Density Lipoprotein ◽  
Human Plasma ◽  
Platelet Rich Plasma ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Free Plasma ◽  
Good Agreement

SummaryHuman plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addition of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma.Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.

scholarly journals Lunasin Improves the LDL-C Lowering Efficacy of Simvastatin via Inhibiting PCSK9 Expression in Hepatocytes and ApoE−/− Mice

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4140 ◽  
Author(s):  
Lili Gu ◽  
Yaqin Gong ◽  
Cheng Zhao ◽  
Yue Wang ◽  
Qinghua Tian ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Low Density Lipoprotein ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Low Density ◽  
Therapeutic Drugs ◽  
Density Lipoprotein Receptor ◽  
Ldl Uptake ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Coa Reductase

Statins are the most popular therapeutic drugs to lower plasma low density lipoprotein cholesterol (LDL-C) synthesis by competitively inhibiting hydroxyl-3-methyl-glutaryl-CoA (HMG-CoA) reductase and up-regulating the hepatic low density lipoprotein receptor (LDLR). However, the concomitant up-regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) by statin attenuates its cholesterol lowering efficacy. Lunasin, a soybean derived 43-amino acid polypeptide, has been previously shown to functionally enhance LDL uptake via down-regulating PCSK9 and up-regulating LDLR in hepatocytes and mice. Herein, we investigated the LDL-C lowering efficacy of simvastatin combined with lunasin. In HepG2 cells, after co-treatment with 1 μM simvastatin and 5 μM lunasin for 24 h, the up-regulation of PCSK9 by simvastatin was effectively counteracted by lunasin via down-regulating hepatocyte nuclear factor 1α (HNF-1α), and the functional LDL uptake was additively enhanced. Additionally, after combined therapy with simvastatin and lunasin for four weeks, ApoE−/− mice had significantly lower PCSK9 and higher LDLR levels in hepatic tissues and remarkably reduced plasma concentrations of total cholesterol (TC) and LDL-C, as compared to each monotherapy. Conclusively, lunasin significantly improved the LDL-C lowering efficacy of simvastatin by counteracting simvastatin induced elevation of PCSK9 in hepatocytes and ApoE−/− mice. Simvastatin combined with lunasin could be a novel regimen for hypercholesterolemia treatment.

scholarly journals Fluorescence studies of protein–sterol relationships in human plasma lipoproteins

1974 ◽  
Vol 137 (2) ◽  
pp. 413-415 ◽  
Author(s):  
Rory J. M. Smith ◽  
Colin Green
Keyword(s):  
High Density Lipoprotein ◽  
Human Plasma ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Tryptophan Fluorescence ◽  
High Density ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Fluorescence Studies ◽  
Esterified Sterols

Cholesta-5,7,9(11)-trien-3β-ol and its oleate ester were incorporated into human low-density lipoprotein and reconstituted high-density lipoprotein. The unesterified sterol was more efficient than its ester in quenching tryptophan fluorescence, especially in low-density lipoprotein. The results, which indicate that in such lipoproteins unesterified sterols are more closely associated with peptide than are esterified sterols, are used to assess possible structures for the lipoproteins.

The glycosphingolipids of human plasma lipoproteins

1981 ◽  
Vol 59 (6) ◽  
pp. 412-417 ◽  
Author(s):  
J. T. R. Clarke
Keyword(s):  
Fabry Disease ◽  
Human Plasma ◽  
Gaucher Disease ◽  
Low Density Lipoprotein ◽  
Physical Stability ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Healthy Individuals ◽  
Neutral Glycosphingolipids ◽  
Low Concentrations

Human plasma contains low concentrations of four neutral glycosphingolipids (glucosylceramide, lactosylceramide, globotriaosylceramide and globotetraosylcerarmide) and GM3 ganglioside which occur as part of the plasma lipoproteins, particularly low density lipoprotein (LDL, d 1.006–1.063 g∙mL−1) and to a lesser extent with high density lipoprotein (HDL, d 1.063–1.21 g∙mL−1). Plasma glucosylceramide appears to exchange freely between plasma lipoproteins and erythrocytes, and probably also between different lipoprotein fractions, in the circulation. Free exchange of other major neutral glycosphingolipids (GSLs) between lipoproteins and erythrocytes, or between lipoprotein fractions, does not normally occur. The GSL profile of each lipoprotein fraction is the same as the overall GSL composition of unfractionated plasma. In Fabry disease and Gaucher disease, GSL storage diseases, the excess glycolipid in plasma is distributed among the various lipoprotein fractions in the same relative proportions as in healthy individuals. In familial hypercholesterolemia, in which the levels of all plasma GSLs are elevated, the excess GSL is largely associated with the increased concentrations of LDL. In patients with hereditary hypolipoproteinemias, the levels of GSL in plasma are decreased less than those of other lipids. The relative excess of GSL in these patients is distributed among the remaining lipoprotein fractions. Excess GSL such as occurs in Fabry disease, does not appear to have a biologically significant effect on the physical stability of human LDL.

scholarly journals Ascorbic acid enhances low-density lipoprotein receptor expression by suppressing proprotein convertase subtilisin/kexin 9 expression

2020 ◽  
Vol 295 (47) ◽  
pp. 15870-15882
Author(s):  
Dandan Wang ◽  
Xiaoxiao Yang ◽  
Yuanli Chen ◽  
Ke Gong ◽  
Maoyun Yu ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Proprotein Convertase ◽  
Acid Supplementation ◽  
Density Lipoprotein Receptor ◽  
Ldl Uptake ◽  
Ascorbic Acid Supplementation

Ascorbic acid, a water-soluble antioxidant, regulates various biological processes and is thought to influence cholesterol. However, little is known about the mechanisms underpinning ascorbic acid-mediated cholesterol metabolism. Here, we determined if ascorbic acid can regulate expression of proprotein convertase subtilisin/kexin 9 (PCSK9), which binds low-density lipoprotein receptor (LDLR) leading to its intracellular degradation, to influence low-density lipoprotein (LDL) metabolism. At cellular levels, ascorbic acid inhibited PCSK9 expression in HepG2 and Huh7 cell lines. Consequently, LDLR expression and cellular LDL uptake were enhanced. Similar effects of ascorbic acid on PCSK9 and LDLR expression were observed in mouse primary hepatocytes. Mechanistically, ascorbic acid suppressed PCSK9 expression in a forkhead box O3-dependent manner. In addition, ascorbic acid increased LDLR transcription by regulating sterol regulatory element-binding protein 2. In vivo, administration of ascorbic acid reduced serum PCSK9 levels and enhanced liver LDLR expression in C57BL/6J mice. Reciprocally, lack of ascorbic acid supplementation in L-gulono-γ-lactone oxidase deficient (Gulo−/−) mice increased circulating PCSK9 and LDL levels, and decreased liver LDLR expression, whereas ascorbic acid supplementation decreased PCSK9 and increased LDLR expression, ameliorating LDL levels in Gulo−/− mice fed a high fat diet. Moreover, ascorbic acid levels were negatively correlated to PCSK9, total and LDL levels in human serum samples. Taken together, these findings suggest that ascorbic acid reduces PCSK9 expression, leading to increased LDLR expression and cellular LDL uptake. Thus, supplementation of ascorbic acid may ameliorate lipid profiles in ascorbic acid-deficient species.

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