scholarly journals High-Density Lipoproteins and the Kidney

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Arianna Strazzella ◽  
Alice Ossoli ◽  
Laura Calabresi

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Scott M Gordon ◽  
Catherine A Reardon ◽  
Godfrey S Getz ◽  
W S Davidson

High density lipoproteins (HDL) are a highly heterogeneous population of particles composed of various lipids and proteins. They have been demonstrated to possess a diverse variety of functional properties which are thought to contribute to protection against cardiovascular disease (CVD). Proteomics studies have identified up to 75 different proteins which can associate with HDL. The basis for the compositional diversity of HDL is not known but a better understanding will yield important information about its broad functional diversity. To investigate the impact of common HDL apolipoproteins on the distribution of other apolipoproteins, we have begun to systematically fractionate plasma from various HDL apolipoprotein KO mice. Plasma from apoA-I, apoA-IV and apoA-II global KO mice was applied to gel filtration chromatography to distinguish HDL size populations. HDL particles sequestered by a phospholipid binding resin were proteomically analyzed by electrospray ionization mass spectrometry. By comparing elution volume shifts (i.e. particle size variations) for each HDL protein between WT controls and the KO models, we assessed the impact of the deleted protein on HDL size distributions. Ablation of apoA-I, while decreasing total HDL phospholipid by 70%, had a surprisingly small impact on the distribution of the majority of other HDL associated proteins - affecting only 9 of them. Genetic apoA-IV ablation had a similar modest effect shifting a distinct subset of 9 proteins. However, loss of apoA-II, in addition to causing a similar 70% reduction in overall HDL phospholipids, affected the size distribution of some 45 HDL proteins (including several complement proteins and paraoxonase-1). These data suggest that apoA-I, while associated with the majority of HDL phospholipid, may actually interact with relatively few of the lower abundance proteins known to be associated with HDL. ApoA-II on the other hand, may interact with many of these, perhaps acting as a docking site or adaptor molecule.


Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 671 ◽  
Author(s):  
Florens ◽  
Calzada ◽  
Delolme ◽  
Page ◽  
Guebre Egziabher ◽  
...  

Chronic kidney disease is associated with an increased cardiovascular risk, and altered biological properties of high-density lipoproteins (HDL) may play a role in these events. This study aimed to describe the HDL proteome from non-diabetic hemodialysis patients and identify potential pathways affected by the dysregulated expression of HDL proteins. HDL were sampled from nine non-diabetic hemodialysis (HD) and eight control patients. Samples were analyzed using a nano-RSLC coupled with a Q-Orbitrap. Data were processed by database searching using SequestHT against a human Swissprot database and quantified with a label-free quantification approach. Proteins that were in at least five of the eight control and six of the nine HD patients were analyzed. Analysis was based on pairwise ratios and the ANOVA hypothesis test. Among 522 potential proteins, 326 proteins were identified to be in the HDL proteome from HD and control patients, among which 10 were significantly upregulated and nine downregulated in HD patients compared to the control patients (p < 0.05). Up and downregulated proteins were involved in lipid metabolism, hemostasis, wound healing, oxidative stress, and apoptosis pathways. This difference in composition could partly explain HDL dysfunction in the chronic kidney disease (CKD) population and participate in the higher cardiovascular risk observed in this population.


2020 ◽  
Vol 7 (2) ◽  
pp. 51
Author(s):  
Rio Khalif Eldiaz ◽  
Agustono Agustono ◽  
Kustiawan Tri Pursetyo

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.


Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Donovan McGrowder ◽  
Cliff Riley ◽  
Errol Y. St. A. Morrison ◽  
Lorenzo Gordon

High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including “healthy” diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.


Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1045
Author(s):  
Naoko Sawada ◽  
Takashi Obama ◽  
Mirei Mizuno ◽  
Kiyoshi Fukuhara ◽  
Sanju Iwamoto ◽  
...  

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.


2021 ◽  
Author(s):  
Kai Liu ◽  
Ralf Nilsson ◽  
Elisa Lázaro-Ibáñez ◽  
Tasso Miliotis ◽  
Michael Lerche ◽  
...  

Abstract Lipid nanoparticles (LNPs) are currently of great interest for therapeutic nucleic acid delivery. Lipid-based nanoparticles are, however, difficult to study analytically and so our understanding of the interaction between LNPs and biological systems remains obscure, particularly in terms of biomolecular corona formation and the impact this has on therapeutic efficacy and targeting. Ideally, we would like to engineer particles to acquire corona components that facilitate targeting, cargo delivery and improved safety. This requires studying the relationship between LNPs, biofluids and the resulting coronas. The particle-corona complexes are, however, fragile and biofluids also contain particles (such as lipoproteins) with sizes and biochemical characteristics similar to lipid nanoparticles, so contamination with biological components is a challenge. Here we describe a rapid, automated, and unbiased isolation method for LNP biomolecular coronas, coupled with proteomic and lipidomic analysis. Using these analytical methods, we systematically studied, in lean and obese rats, the variation in LNP-mediated mRNA delivery caused by individual physiology. A comprehensive multivariate model links LNP corona content to efficacy, identifying and validating high-density lipoproteins as a previously unidentified factor affecting particle efficacy.


2021 ◽  
Author(s):  
Arnold von Eckardstein

AbstractLow plasma levels of High Density Lipoprotein (HDL) cholesterol (HDL-C) are associated with increased risks of atherosclerotic cardiovascular disease (ASCVD). In cell culture and animal models, HDL particles exert multiple potentially anti-atherogenic effects. However, drugs increasing HDL-C have failed to prevent cardiovascular endpoints. Mendelian Randomization studies neither found any genetic causality for the associations of HDL-C levels with differences in cardiovascular risk. Therefore, the causal role and, hence, utility as a therapeutic target of HDL has been questioned. However, the biomarker “HDL-C” as well as the interpretation of previous data has several important limitations: First, the inverse relationship of HDL-C with risk of ASCVD is neither linear nor continuous. Hence, neither the-higher-the-better strategies of previous drug developments nor previous linear cause-effect relationships assuming Mendelian randomization approaches appear appropriate. Second, most of the drugs previously tested do not target HDL metabolism specifically so that the futile trials question the clinical utility of the investigated drugs rather than the causal role of HDL in ASCVD. Third, the cholesterol of HDL measured as HDL-C neither exerts nor reports any HDL function. Comprehensive knowledge of structure-function-disease relationships of HDL particles and associated molecules will be a pre-requisite, to test them for their physiological and pathogenic relevance and exploit them for the diagnostic and therapeutic management of individuals at HDL-associated risk of ASCVD but also other diseases, for example diabetes, chronic kidney disease, infections, autoimmune and neurodegenerative diseases.


1992 ◽  
Vol 281 (3) ◽  
pp. 851-857 ◽  
Author(s):  
I J Martins ◽  
T G Redgrave

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.


1979 ◽  
Vol 42 (04) ◽  
pp. 1181-1186 ◽  
Author(s):  
A Nordøy ◽  
Nina Refsum ◽  
D Thelle ◽  
S Jæger

SummaryTwo groups of healthy male subjects one with low (mean 1.03 mmol/1), and the other with normal (mean 1.80 mmol/1), concentrations of high density lipoprotein (HDL) cholesterol in plasma were investigated. A series of in vitro platelet function tests were performed in order to investigate a possible connection between low HDL concentration, which has been defined as an independent risk factor for the occurrence of CHD, and disturbances in platelet function.No significant differences in platelet function were observed between the two groups. A positive correlation was found between platelet factor 3 activity both in platelet rich and platelet poor plasma and the plasma concentration of HDL.


Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 549
Author(s):  
Andrea Bonnin Márquez ◽  
Sumra Nazir ◽  
Emiel P.C. van der Vorst

High-density lipoprotein (HDL) is well-known for its cardioprotective effects, as it possesses anti-inflammatory, anti-oxidative, anti-thrombotic, and cytoprotective properties. Traditionally, studies and therapeutic approaches have focused on raising HDL cholesterol levels. Recently, it became evident that, not HDL cholesterol, but HDL composition and functionality, is probably a more fruitful target. In disorders, such as chronic kidney disease or cardiovascular diseases, it has been observed that HDL is modified and becomes dysfunctional. There are different modification that can occur, such as serum amyloid, an enrichment and oxidation, carbamylation, and glycation of key proteins. Additionally, the composition of HDL can be affected by changes to enzymes such as cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and phospholipid transfer protein (PLTP) or by modification to other important components. This review will highlight some main modifications to HDL and discuss whether these modifications are purely a consequential result of pathology or are actually involved in the pathology itself and have a causal role. Therefore, HDL composition may present a molecular target for the amelioration of certain diseases, but more information is needed to determine to what extent HDL modifications play a causal role in disease development.


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