High Density Lipoproteins: Is There a Comeback as a Therapeutic Target?

Hdl Metabolism ◽

Relationship Of

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.

High-density lipoproteins, inflammation and oxidative stress

Clinical Science ◽

10.1042/cs20080106 ◽

2008 ◽

Vol 116 (2) ◽

pp. 87-98 ◽

Cited By ~ 95

Author(s):

Fatiha Tabet ◽

Kerry-Anne Rye

Keyword(s):

Disease Risk ◽

Antioxidant Properties ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Epidemiological Studies ◽

High Density ◽

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.

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

Biomedicines ◽

10.3390/biomedicines9080857 ◽

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 ◽

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) [...]

High-Density Lipoproteins and the Kidney

Cells ◽

10.3390/cells10040764 ◽

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 ◽

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.

Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism

Scientific Reports ◽

10.1038/s41598-019-51367-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Kenji Nishimura ◽

Taichi Murakami ◽

Toshihiro Sakurai ◽

Masashi Miyoshi ◽

Kiyoe Kurahashi ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Insulin Resistant ◽

Cell Dysfunction ◽

Fractionation Analysis ◽

Abnormal Lipid Metabolism ◽

Hdl Metabolism ◽

Relationship Of

Abstract Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = −0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.

High-Density Lipoprotein (HDL) Triglyceride and Oxidized HDL: New Lipid Biomarkers of Lipoprotein-Related Atherosclerotic Cardiovascular Disease

Antioxidants ◽

10.3390/antiox9050362 ◽

2020 ◽

Vol 9 (5) ◽

pp. 362 ◽

Cited By ~ 1

Author(s):

Fumiaki Ito ◽

Tomoyuki Ito

Keyword(s):

Cardiovascular Disease ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Peroxide ◽

Hdl Cholesterol ◽

High Density ◽

Lipid Panel ◽

Lipid Markers ◽

Dysfunctional Hdl

Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as a metric of HDL quantity, is inversely associated with cardiovascular disease, independent of LDL-C. However, the quality of the HDL appears to be more important than its quantity, because HDL loses its antiatherogenic functions due to changes in its composition and becomes “dysfunctional HDL”. Although there is evidence of the existence of “dysfunctional HDL”, biomarkers for monitoring dysfunctional HDL in clinical practice have not yet been established. In this review, we propose a new lipid panel for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease. The lipid panel includes the measurement of lipid peroxide and triglyceride contents within HDL particles.

Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis

Lipids in Health and Disease ◽

10.1186/s12944-019-1170-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Tianhua Zhang ◽

Jin Chen ◽

Xiaoyu Tang ◽

Qin Luo ◽

Danyan Xu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Adipose Tissue ◽

Hormone Secretion ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Nutritional Disorder ◽

Hdl Function ◽

And Function

AbstractObesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

The Content of Low Density Lipoprotein, High Density Lipoproteins, Cholesterol on Pen Shells (Atrina Pectinata) Fish Catch in Kenjeran Surabaya

Journal of Marine and Coastal Science ◽

10.20473/jmcs.v7i2.20713 ◽

2020 ◽

Vol 7 (2) ◽

pp. 51

Author(s):

Rio Khalif Eldiaz ◽

Agustono Agustono ◽

Kustiawan Tri Pursetyo

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Low Density ◽

Digestive Organs ◽

Cholesterol Levels ◽

Fish Catch ◽

Atrina Pectinata

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.

Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery

International Journal of Molecular Sciences ◽

10.3390/ijms21030739 ◽

2020 ◽

Vol 21 (3) ◽

pp. 739 ◽

Cited By ~ 4

Author(s):

Jiansheng Huang ◽

Dongdong Wang ◽

Li-Hao Huang ◽

Hui Huang

Keyword(s):

Cardiovascular Disease ◽

High Density Lipoprotein ◽

Cholesterol Efflux ◽

Density Lipoprotein ◽

Inverse Correlation ◽

Hdl Cholesterol ◽

High Density ◽

New Paradigm

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

Dysfunctional high-density lipoprotein: the role of myeloperoxidase and paraoxonase-1

Current Medicinal Chemistry ◽

10.2174/0929867327999200716112353 ◽

2020 ◽

Vol 27 ◽

Cited By ~ 1

Author(s):

Tiziana Bacchetti ◽

Gianna Ferretti ◽

Federico Carbone ◽

Stefano Ministrini ◽

Fabrizio Montecucco ◽

...

Keyword(s):

Metabolic Syndrome ◽

Protective Factor ◽

Density Lipoprotein ◽

High Density ◽

Paraoxonase 1 ◽

Potential Marker ◽

And Function

: Low circulating high-density lipoproteins (HDL) are not only a defining criteria for metabolic syndrome, but are more generally associated with atherosclerotic cardiovascular disease (ASCVD) and other chronic diseases. Oxidative stress, a hallmark of cardio-metabolic disease, further influences HDL activity by suppressing their function. Especially the leukocyte-derived enzyme myeloperoxidase (MPO) has recently attracted great interest as it catalyzes the formation of oxidizing reactive species that modify the structure and function of HDL, ultimately increasing cardiovascular risk. Contrariwise, paraoxonase-1 (PON1) is an HDL-associated enzyme that protects HDL from lipid oxidation, and then acts as a protective factor against ASCVD. Noteworthy, recent studies have demonstrated how MPO, PON1 and HDL form a functional complex in which PON1 partially inhibits the MPO activity, while MPO in turn partially inactivates PON1.In line with that, high MPO/PON1 ratio characterizes patients with ASCVD and metabolic syndrome and has been suggested as a potential marker of dysfunctional HDL as well as a predictor of ASCVD. In this review, we summarize the evidence on the interactions between MPO and PON1 with regard to their structure, function and interaction with HDL activity. We also provide an overview on in vitro and experimental animal models, finally focusing on clinical evidence from cohort of patients with ASCVD and metabolic syndrome.

The Role of High-Density Lipoproteins in Reducing the Risk of Vascular Diseases, Neurogenerative Disorders, and Cancer

Cholesterol ◽

10.1155/2011/496925 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 36

Author(s):

Donovan McGrowder ◽

Cliff Riley ◽

Errol Y. St. A. Morrison ◽

Lorenzo Gordon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Current Knowledge ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Protective Effects ◽

Anti Oxidant ◽

Anti Inflammatory

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.