scholarly journals Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2730 ◽  
Author(s):  
Diego Estrada-Luna ◽  
María Ortiz-Rodriguez ◽  
Lizett Medina-Briseño ◽  
Elizabeth Carreón-Torres ◽  
Jeannett Izquierdo-Vega ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Density Lipoprotein ◽  
Protein Composition ◽  
Inverse Correlation ◽  
Epidemiological Studies ◽  
High Density ◽  
High Density Lipoproteins ◽  
Current Therapies ◽  
The Impact

High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.

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.

The biological activity of high-density lipoprotein fractions and their role in the development of cardiovascular diseases

2016 ◽  
Vol 88 (9) ◽  
pp. 111-118 ◽  
Author(s):  
Ya D Babintseva ◽  
L Camont ◽  
J Chapman ◽  
M Lhomme ◽  
V P Karagodin ◽  
...  
Keyword(s):  
Biological Activity ◽  
Cardiovascular Diseases ◽  
Density Lipoprotein ◽  
Compositional Analysis ◽  
Biological Properties ◽  
High Density ◽  
High Density Lipoproteins ◽  
Pharmacological Targets ◽  
New Findings ◽  
Protein Rich

Increasing the human plasma concentration of high-density lipoproteins (HDL) may be part of strategy for control of cardiovascular diseases (CVD). HDL particles vary in their structure, metabolism, and biological activity. The review describes major HDL fractions (subpopulations) and discusses new findings on the antiatherogenic properties of HDL particles. The whole spectrum of HDL fractions, small, dense, protein-rich lipoproteins, has atheroprotective properties that are determined by the presence of specialized groups of proteins and lipids; however, this activity may be decreased in atherogenic lesion. Comprehensive structural and compositional analysis of HDL may provide key information to identify the fractions that have characteristic biological properties and lose their functionality in CVD. These fractions may be also biomarkers for the risk of CVD and hence represent pharmacological targets.

scholarly journals An obesity model and corona multiomics analysis reveal high-density lipoprotein effects on lipid nanoparticle function

2021 ◽  
Author(s):  
Kai Liu ◽  
Ralf Nilsson ◽  
Elisa Lázaro-Ibáñez ◽  
Tasso Miliotis ◽  
Michael Lerche ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Lipid Nanoparticles ◽  
High Density ◽  
High Density Lipoproteins ◽  
Nucleic Acid Delivery ◽  
Cargo Delivery ◽  
Corona Formation ◽  
Obese Rats ◽  
The Impact ◽  
The Relationship

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.

scholarly journals Protection against Glucolipotoxicity by High Density Lipoprotein in Human PANC-1 Hybrid 1.1B4 Pancreatic Beta Cells: The Role of microRNA

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 218
Author(s):  
Jamie M.R. Tarlton ◽  
Richard J. Lightbody ◽  
Steven Patterson ◽  
Annette Graham
Keyword(s):  
High Density Lipoprotein ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Model ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Microrna Profile ◽  
Altered Gene ◽  
The Impact

High-density lipoproteins provide protection against the damaging effects of glucolipotoxicity in beta cells, a factor which sustains insulin secretion and staves off onset of type 2 diabetes mellitus. This study examines epigenetic changes in small non-coding microRNA sequences induced by high density lipoproteins in a human hybrid beta cell model, and tests the impact of delivery of a single sequence in protecting against glucolipotoxicity. Human PANC-1.1B4 cells were used to establish Bmax and Kd for [3H]cholesterol efflux to high density lipoprotein, and minimum concentrations required to protect cell viability and reduce apoptosis to 30mM glucose and 0.25 mM palmitic acid. Microchip array identified the microRNA signature associated with high density lipoprotein treatment, and one sequence, hsa-miR-21-5p, modulated via delivery of a mimic and inhibitor. The results confirm that low concentrations of high-density lipoprotein can protect against glucolipotoxicity, and report the global microRNA profile associated with this lipoprotein; delivery of miR-21-5p mimic altered gene targets, similar to high density lipoprotein, but could not provide sufficient protection against glucolipotoxicity. We conclude that the complex profile of microRNA changes due to HDL treatment may be difficult to replicate using a single microRNA, findings which may inform current drug strategies focused on this approach.

scholarly journals High Density Lipoproteins and Diabetes

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 850
Author(s):  
Blake J. Cochran ◽  
Kwok-Leung Ong ◽  
Bikash Manandhar ◽  
Kerry-Anne Rye
Keyword(s):  
Potential Role ◽  
Unmet Need ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
High Plasma ◽  
High Density ◽  
High Density Lipoproteins ◽  
Established Disease ◽  
Plasma High Density ◽  
The Subject

Epidemiological studies have established that a high plasma high density lipoprotein cholesterol (HDL-C) level is associated with reduced cardiovascular risk. However, recent randomised clinical trials of interventions that increase HDL-C levels have failed to establish a causal basis for this relationship. This has led to a shift in HDL research efforts towards developing strategies that improve the cardioprotective functions of HDLs, rather than simply increasing HDL-C levels. These efforts are also leading to the discovery of novel HDL functions that are unrelated to cardiovascular disease. One of the most recently identified functions of HDLs is their potent antidiabetic properties. The antidiabetic functions of HDLs, and recent key advances in this area are the subject of this review. Given that all forms of diabetes are increasing at an alarming rate globally, there is a clear unmet need to identify and develop new approaches that will complement existing therapies and reduce disease progression as well as reverse established disease. Exploration of a potential role for HDLs and their constituent lipids and apolipoproteins in this area is clearly warranted. This review highlights focus areas that have yet to be investigated and potential strategies for exploiting the antidiabetic functions of HDLs.

Analysis of Prognostic Significance of Serum HDL Level in Patients of Sepsis Admitted to a Tertiary Care Hospital of Southern Odisha

2021 ◽  
Vol 8 (38) ◽  
pp. 3384-3389
Author(s):  
Umashankar Mishra ◽  
Sudhansu Sekhar Pradhan ◽  
Srabani Pradhan
Keyword(s):  
Tertiary Care ◽  
Prognostic Significance ◽  
Density Lipoprotein ◽  
Inverse Correlation ◽  
Hdl Cholesterol ◽  
Clinical History ◽  
High Density ◽  
Initial Assessment ◽  
High Density Lipoproteins ◽  
Care Hospital

BACKGROUND Sepsis is the body’s overwhelming and life-threatening response to infection that may cause tissue damage, organ failure and death. High density lipoproteins (HDL) are relevant players in both innate and adaptive immunity involved in response to infection. So, with this reference and limited number of studies showing association of prognosis with high-density lipoprotein level in sepsis patients, this study was done to find out the changes in HDL level of sepsis patients and its association with prognosis. METHODS This is a prospective hospital-based study done on 210 patients with sepsis admitted in medicine ward and intensive care unit (ICU) of M.K.C.G Medical College, Odisha from November 2017 to November 2019. Patient’s included in study are based on initial assessment by quick SOFA (Qsofa) scoring system. At the time of admission, patient’s clinical history, relevant biochemical parameters were noted and detail clinical examination was done. All the patients were followed prospectively during their entire course of stay. Serum HDL was done on the day of admission and was repeated on day 4 and on day of discharge. Outcome was measured in terms of survival and duration of hospital stay. RESULTS Out of 210 patients, 168 (80 %) survived and 42 (20 %) cases died. Survival rate was significantly higher in patients admitted to ward than those in ICU. HDL level on day 1 showed significant inverse correlation with SOFA score. Inverse correlation was also observed between the duration of stay in hospital and HDL on day 1. Significantly higher level of HDL was observed in patients who survived than non-survivors. In cases which survived, a statistically significant increase was observed in HDL level from day 1 to day of discharge. CONCLUSIONS HDL cholesterol on day of admission can be viewed as a significant predictor of mortality in patients of sepsis. KEYWORDS HDL, sepsis, prognosis, qSOFA, SOFA

High-density lipoproteins, inflammation and oxidative stress

2008 ◽  
Vol 116 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Fatiha Tabet ◽  
Kerry-Anne Rye
Keyword(s):  
Disease Risk ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
High Density ◽  
High Density Lipoproteins ◽  
Atherosclerotic Cardiovascular Disease ◽  
Transport Pathway ◽  
Anti Inflammatory

Plasma levels of HDL (high-density lipoprotein)-cholesterol are strongly and inversely correlated with atherosclerotic cardiovascular disease. Both clinical and epidemiological studies have reported an inverse and independent association between serum HDL-cholesterol levels and CHD (coronary heart disease) risk. The cardioprotective effects of HDLs have been attributed to several mechanisms, including their involvement in the reverse cholesterol transport pathway. HDLs also have antioxidant, anti-inflammatory and antithrombotic properties and promote endothelial repair, all of which are likely to contribute to their ability to prevent CHD. The first part of this review summarizes what is known about the origins and metabolism of HDL. We then focus on the anti-inflammatory and antioxidant properties of HDL and discuss why these characteristics are cardioprotective.

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