scholarly journals Artificial High Density Lipoprotein Nanoparticles in Cardiovascular Research

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2829 ◽  
Author(s):  
Kornmueller ◽  
Vidakovic ◽  
Prassl
Keyword(s):  
Self Assembly ◽  
Density Lipoprotein ◽  
Medical Diagnostics ◽  
High Density ◽  
High Density Lipoproteins ◽  
Special Focus ◽  
Structural Determinants ◽  
Cardiovascular Research ◽  
Recent Developments ◽  
Apo Ai

Lipoproteins are endogenous nanoparticles which are the major transporter of fats and cholesterol in the human body. They play a key role in the regulatory mechanisms of cardiovascular events. Lipoproteins can be modified and manipulated to act as drug delivery systems or nanocarriers for contrast agents. In particular, high density lipoproteins (HDL), which are the smallest class of lipoproteins, can be synthetically engineered either as nascent HDL nanodiscs or spherical HDL nanoparticles. Reconstituted HDL (rHDL) particles are formed by self-assembly of various lipids and apolipoprotein AI (apo-AI). A variety of substances including drugs, nucleic acids, signal emitting molecules, or dyes can be loaded, making them efficient nanocarriers for therapeutic applications or medical diagnostics. This review provides an overview about synthesis techniques, physicochemical properties of rHDL nanoparticles, and structural determinants for rHDL function. We discuss recent developments utilizing either apo-AI or apo-AI mimetic peptides for the design of pharmaceutical rHDL formulations. Advantages, limitations, challenges, and prospects for clinical translation are evaluated with a special focus on promising strategies for the treatment and diagnosis of atherosclerosis and cardiovascular diseases.

Structural and functional assessment of high-density lipoprotein heterogeneity

1994 ◽  
Vol 40 (8) ◽  
pp. 1554-1558 ◽  
Author(s):  
M Dobiásová ◽  
J J Frohlich
Keyword(s):  
Low Density Lipoprotein ◽  
Plasma Concentrations ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Risk Groups ◽  
Study Groups ◽  
High Density ◽  
High Density Lipoproteins ◽  
Apo Ai

Abstract We studied the heterogeneity of high-density lipoproteins (HDL) in plasma of 110 subjects, using three different methods: (a) gradient gel electrophoresis (GGE); (b) electroimmunoassay, to measure the concentration of lipoprotein particles containing apoprotein (apo) AI but no apo-AII (LP AI); and (c) cholesterol esterification rate (FERHDL) in very-low- and low-density lipoprotein-depleted plasma. There were two study groups: patients with hypertension, whose plasma lipid profile was similar to their respective controls, and patients with hypoalphalipoproteinemia (hypoalpha), whose family members served as controls. Values for FERHDL were significantly higher in both risk groups than in their respective controls. LP AI was significantly decreased only in the hypoalpha subjects. Generally, LP AI and FERHDL were inversely related. LP AI correlated strongly with plasma HDL-cholesterol, apo AI, and LP AI/AII; FERHDL correlated with those values inversely. LP AI, but not FERHDL, correlated with HDL free cholesterol. On the other hand, FERHDL correlated strongly with plasma concentrations of triglycerides and with the plasma ratio of total/HDL-cholesterol while LP AI did not. GGE determination of the composition of HDL subspecies showed that both FERHDL and LP AI were significantly related to the content of HDL2b particles: FERHDL inversely, LP AI directly; the relative amount of HDL3b,c particles correlated only with FERHDL. We conclude that GGE and FERHDL can be used to quantify both the apparently protective (HDL2b) and risk-associated (HDL3b,c) particles, whereas the concentration of LP AI in plasma mainly reflects the concentration of the HDL2 subpopulation.

scholarly journals High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad and the Future

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 857
Author(s):  
Josep Julve ◽  
Joan Carles Escolà-Gil
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
High Density ◽  
High Density Lipoproteins ◽  
Atherosclerotic Cardiovascular Disease ◽  
Plasma High Density ◽  
Low Levels

Epidemiological studies have shown that low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with increased atherosclerotic cardiovascular disease (CVD) [...]

scholarly journals High-Density Lipoproteins and the Kidney

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Arianna Strazzella ◽  
Alice Ossoli ◽  
Laura Calabresi
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Lcat Deficiency ◽  
Progression Of Renal Disease ◽  
The Impact

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.

Abstract 260: Knockout of Apolipoprotein A-II Has Dramatic Effects on High-Density Lipoprotein Subspecies Distribution

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Scott M Gordon ◽  
Catherine A Reardon ◽  
Godfrey S Getz ◽  
W S Davidson
Keyword(s):  
Gel Filtration ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Ionization Mass ◽  
Associated Proteins ◽  
Compositional Diversity ◽  
The Impact ◽  
Modest Effect

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.

Involvement of high-density lipoprotein in stimulatory effect of hormones supporting function of the bovine corpus luteum.

2003 ◽  
Vol 51 (1) ◽  
pp. 111-120 ◽  
Author(s):  
D. Skarżyński ◽  
J. Młynarczuk ◽  
J. Kotwica
Keyword(s):  
Luteinising Hormone ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Luteal Cells ◽  
Progesterone Secretion ◽  
Bovine Corpus Luteum ◽  
Progesterone Synthesis ◽  
Deficient Medium ◽  
Intracellular Pathway

The hypothesis that epinephrine (noradrenaline, NA) enhances utilisation of high-density lipoproteins (HDL) by bovine luteal cells and that this process involves phospholipase (PL) C and protein kinase (PK) C intracellular pathway was tested. Luteal cells from days 2-4, 5-10 or 11-17 of the oestrous cycle were pre-incubated for 20h. Subsequently DMEM/Ham's F-12 medium was replaced by fresh medium and the cells were treated for 6 h as follows: In Experiment I with HDL (5-75μg cholesterol per ml), NA, isoprenaline (ISO) or luteinising hormone (LH). In Experiment II cells were incubated for further 24h in deficient medium (without FCS) and next treated as in Experiment I. In Experiment III cells were stimulated with NA, ISO or LH alone and together with HDL. In Experiment IV cells were treated with PLC inhibitor (U-73122) or with PKC inhibitor (staurosporine) or stimulator (phorbol 12-myristrate 13-acetate) and with either NA, insulin or LH. Only luteal cells from days 5-10 of the cycle responded on HDL and β-mimetics (P<0.05). LH stimulated progesterone secretion from the luteal cells during all stages of the cycle (P<0.001). Cells incubated in deficient medium and supplemented with HDL secreted as much progesterone as those stimulated by LH in all stages of the cycle. Beta-mimetics were unable to enhance the stimulatory effect of HDL. Blockade of PLC had no influence on progesterone secretion from cells treated with either NA or LH, but this did impair the stimulatory effect of insulin (P<0.05). Similarly, blockade of PKC by staurosporine impaired (P<0.05) the effect of insulin only but not that observed after LH or NA treatment. We suggest that: (a) noradrenergic stimulation does not enhance utilisation of cholesterol from HDL for progesterone secretion; (b) the fasting of luteal cells seems to activate enzymes responsible for the progesterone synthesis; (c) effect of NA on progesterone secretion from luteal cells does not involve the PLC-PKC pathway.

Abstract 617: Intestine-Specific MTP Deficiency with ACAT2 Gene Ablation Lowers Acute Cholesterol Absorption With Chylomicrons and High-Density Lipoproteins

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jahangir Iqbal ◽  
Mohamed Boutjdir ◽  
Lawrence L Rudel ◽  
M Mahmood Hussain
Keyword(s):  
Density Lipoprotein ◽  
Microsomal Triglyceride Transfer Protein ◽  
Cholesterol Absorption ◽  
High Density ◽  
High Density Lipoproteins ◽  
High Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Triglyceride Accumulation ◽  
Abca1 Expression ◽  
Deficient Mice

Intestinal cholesterol absorption involves chylomicron and high density lipoprotein (HDL) pathways. Microsomal triglyceride transfer protein (MTP) and ATP binding cassette family A protein 1 (ABCA1) are critical for cholesterol transport by these pathways, respectively. Additionally, acyl Co-A:cholesterol acyltransferase 2 (ACAT2) plays an important role in cholesterol absorption. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their acute absorption. In contrast, ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption. Individual deficiencies of ACAT2 and MTP reduced cholesterol absorption with chylomicrons. We hypothesized that their combined deficiency would increase cholesterol secretion with HDL; unexpectedly, their deficiency reduced secretion with both chylomicrons and HDL. Further, we observed significant reductions in intestinal ABCA1 expression in combined deficient mice. Thus, free cholesterol is unavailable for secretion by the HDL pathway in these mice. We speculate that reductions in ABCA1 expression and HDL secretion might be secondary to massive triglyceride accumulation associated with intestinal MTP deficiency. Besides its role in cholesterol absorption, ACAT2 deficiency causes mild hypertriglyceridemia and reduces steatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in ACAT2 deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid steatosis. Therefore, ACAT2 inhibition might avert steatosis associated with high cholesterol diets by increasing MTP expression.

Abstract 631: Lipid Composition of Gold Nanoparticle-Templated High-Density Lipoprotein Analogs Dictates Cholesterol Efflux Function

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
R Kannan Mutharasan ◽  
Amritha T Singh ◽  
Kaylin M McMahon ◽  
C Shad Thaxton
Keyword(s):  
Fatty Acid ◽  
Lipid Content ◽  
Lipid Composition ◽  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Lipid Membrane ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Transport

Background: Reverse cholesterol transport, the process by which cholesterol is effluxed from cells to high-density lipoproteins (HDL) and is delivered to the liver for clearance, is a promising pathway to augment for treatment of atherosclerosis. Though structure-function relationships for nascent, discoidal HDL and cholesterol efflux have been well studied, how the lipid composition of spherical HDL species - which varies in pathophysiological conditions - impacts their ability to mediate cholesterol efflux has not been investigated. Methods and Results: Spherical gold nanoparticles (5 nm) were used to synthesize spherical HDL analogs (HDL-NP) by adding ApoAI protein, and various lipids. With this strategy a panel of HDL-NP varying in lipid content was generated. HDL-NP designs tested include: dipalmitylphosphatidylcholine (DPPC, saturated fatty acid), dioleoylphosphatidylcholine (DOPC, unsaturated fatty acid), sphingomyelin, lysophosphatidylcholine (LPC), and mixtures thereof. All of these species are found in natural HDL. After characterizing protein and lipid stoichiometry of the purified HDL-NP, these HDL-NP designs were tested in the cellular reverse cholesterol transport assay using J774 mouse macrophages. These studies demonstrate that all HDL-NP designs mediate more efflux than equimolar amounts of ApoAI protein control, and further demonstrate that HDL-NP designs incorporating unsaturated phospholipid (DOPC), sphingomyelin, and LPC - each of which can increase disorder in the lipid membrane and thus give rise to opportunity for cholesterol to intercalate and bind - enhance cholesterol efflux compared to saturated phospholipid (DPPC) design. Conclusion: In summary, these results demonstrate that lipid content of HDL-NP - analogs of spherical HDL - dictates cholesterol efflux function, a finding which sheds light on the functional importance of lipid content variation seen in mature, spherical HDL species.

Determination of high-density lipoprotein phospholipids in serum.

1980 ◽  
Vol 26 (9) ◽  
pp. 1275-1277 ◽  
Author(s):  
Y Yamaguchi
Keyword(s):  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Mean Value ◽  
High Density ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Color Development ◽  
The Mean

Abstract I describe a method for measuring high-density lipoprotein phospholipids. Magnesium chloride and dextran sulfate are used to precipitate all low-density and very-low-density lipoproteins. The supernate contains only high-density lipoproteins, the phospholipid concentration of which is determined by an enzymic method. The precision of the method (CV) is 2.35% (10 repeated assays), and the mean value for HDL-phospholipids was 1006 (SD 248) mg/L for 30 apparently healthy subjects. I used electrophoresis and enzymic color development to confirm the presence of HDL-phospholipids. Results are compared with those obtained by an ultracentrifugation method.

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 &lt; 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 &lt; 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 &lt; 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.

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