The glycosphingolipids of human plasma lipoproteins

1981 ◽  
Vol 59 (6) ◽  
pp. 412-417 ◽  
Author(s):  
J. T. R. Clarke

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.

1976 ◽  
Vol 35 (01) ◽  
pp. 178-185 ◽  
Author(s):  
Helena Sandberg ◽  
Lars-Olov Andersson

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.


1974 ◽  
Vol 137 (2) ◽  
pp. 413-415 ◽  
Author(s):  
Rory J. M. Smith ◽  
Colin Green

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.


2014 ◽  
Vol 111 (03) ◽  
pp. 518-530 ◽  
Author(s):  
Monireh Dashty ◽  
Mohammad Motazacker ◽  
Johannes Levels ◽  
Marcel de Vries ◽  
Morteza Mahmoudi ◽  
...  

SummaryApart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL-and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti-microbial proteins. Prothrombin, protein S, fibrinogen γ, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen α chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 – dyslipidaemia, 2 – atherosclerosis and vascular disease, and 3 – coagulation disorders.


1988 ◽  
Vol 34 (2) ◽  
pp. 240-243 ◽  
Author(s):  
J M Ruiz-Albusac ◽  
E Velázquez ◽  
A Montes

Abstract We studied the precipitation of isolated lipoproteins with heparin and MnCl2. Lipoproteins were isolated from human plasma by preparative ultracentrifugation and their free cholesterol was labeled. Each lipoprotein fraction was then precipitated at various pHs, with or without bovine serum albumin (60 g/L) present. Under no set of conditions was one class of lipoproteins completely separated from the other two. Specifically, under standard conditions for precipitation of serum lipoproteins (pH 7.4 and protein 60 g/L), 12% of the very-low-density lipoprotein (VLDL) and 8% of the low-density lipoprotein (LDL) remained in the supernatant liquid, and 30% of the high-density lipoprotein (HDL) was precipitated. These results indicate that, under these conditions, so-called HDL cholesterol may be a mixture of VLDL, LDL, and HDL, although the sum of the amount of these three fractions remaining in the supernate is fortuitously very close to the value for HDL cholesterol isolated by ultracentrifugation.


Author(s):  
Aikaterini N. Tsouka ◽  
Alexandros D. Tselepis

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.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Thanvi ◽  
P Thakkar

Abstract Funding Acknowledgements Type of funding sources: None. Introduction   Cardiovascular disease (CVD) including heart disease and stroke, is the leading cause of death globally and in India.  The importance of primary prevention, defined as interventions designed to modify adverse risk factors with the goal of preventing an initial CVD event has been established beyond doubt by several population based studies in healthy individuals. While there have been many studies defining the high prevalence in CVD risk factors in Indian population, this study sought to determine the prevalence of undiagnosed modifiable CVD risk factors in healthy individuals.  Methods The  cross sectional, analytical study was carried out at the hospitals, from 1st April 2015 to 31st dec 2017. Subjects between 18 - 70 years of age who were healthy and were undergoing health checkup were included in the study. A total of 5000 patients were screened, those having existing CVD risk factors were excluded from the study.  This study was approved by the institutional ethics committee of the hospital. Written informed consent was obtained from all subjects. The data collection record sheet was prepared based on validated and standardized questionnaires which was used to enter all data.  Physical examination for vitals and BMI was done by qualified physicians. Blood investigations were done for diabetes and dyslipidemia and thyroid dysfunction. ACC/AHA criteria was used for diagnosis of  hypertension, ADA criteria for diabetes. Joint British society 3 risk score and ASCVD risk score was calculated using standard calculators. Results At screening, 4998 participants aged ≥18 years were approached to participate in study. The study population included 2705 men (68.1%) and 1265 women (31.9%) with a mean age of 68± 18.8 years. The most prevalent risk factor was overweight and obesity (71.2%). The prevalence of undiagnosed HTN was 73.3%, undiagnosed pre-diabetes was 24.9% and undiagnosed diabetes was 28.3%. Out of total, 44.3% subjects had high level of low-density lipoprotein and 36.6% subjects had low level of high-density lipoprotein, 20.1% subjects had high level of very-low density lipoprotein (VLDL) and 17.3% subjects had high level of triglyceride. Tobacco smoking was present in 7.7% of the population. The risk estimation predicted 29.1% of the study participants to have more than 10% risk of heart attack/stroke risk at 10 years. Conclusion Our study reveals a fairly good snapshot of CVDs risk factors in healthy general population. Increased prevalence of high BMI, undiagnosed HTN, diabetes, dyslipidemia was present in our study population.  The population had significantly high predicted risk of heart attack/stroke. These findings warrant the need of community based life style modifications, regular health checkup for healthy population for early detection and modification of CVD risk factors.


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