scholarly journals High-density lipoprotein’s vascular protective functions in metabolic and cardiovascular disease – could extracellular vesicles be at play?

2020 ◽  
Vol 134 (22) ◽  
pp. 2977-2986
Author(s):  
Jack D. Beazer ◽  
Patamat Patanapirunhakit ◽  
Jason M.R. Gill ◽  
Delyth Graham ◽  
Helen Karlsson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Lipid Bilayers ◽  
Extracellular Vesicles ◽  
Metabolic Diseases ◽  
Biological Effects ◽  
High Density ◽  
Vascular Protection ◽  
Hdl Function ◽  
And Function

Abstract High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health – including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases – both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDL’s vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.

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

2019 ◽  
Vol 18 (1) ◽  
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 ◽  
Atherosclerotic Cardiovascular Disease ◽  
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.

scholarly journals The Role of level and function of High Density Lipoprotein (HDL) in Cardiovascular Diseases

2020 ◽  
pp. 118-127
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Inverse Relationship ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
High Density ◽  
Peripheral Tissues ◽  
Hdl Function

High-density lipoprotein (HDL) is a set of particles with heterogeneous structures that have different functions due to various compounds including surface charge, size, lipid, and protein compounds. Several prospective epidemiological studies have demonstrated that there is a clear inverse relationship between serum HDL concentration and risk of coronary heart disease, despite this relationship, clinical evidence has only challenged the usefulness of higher levels of HDL-C in predicting the risk of cardiovascular diseases (CVD) and have proven that the structure of HDL is altered and loosed function. Therefore, extensive research is needed to identify new agents and biomarkers to improve HDL function and reduce the risk of cardiovascular disease. Given that the most important function of HDL is to transfer excess cholesterol from peripheral tissues and macrophage cells through a receptor called ABCA1 and direct it to the liver, plays an important role in protecting the formation of atherosclerotic plaque. This molecule can provide a strong protective effect against oxidative damage caused by free radicals with intermittent inhibition of the production of pro-inflammatory oxidized lipids in the intima layer of arteries. There is an inverse relationship between the ability to efflux cholesterol and the prevalence of CVD. The ability to remove cholesterol from macrophages by HDL, it is a crucial criterion for determining HDL performance, and it has a strong inverse relationship with carotid intima-media thickness and coronary artery stenosis in angiography independent of HDL level. Key Words: High Density Lipoprotein; Cardiovascular Disease; Atherosclerosis; Lipoprotein

scholarly journals Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Annelene Govindsamy ◽  
Strinivasen Naidoo ◽  
Marlon E. Cerf
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Transcription Factors ◽  
Cardiac Development ◽  
Insulin Signalling ◽  
Life Stages ◽  
Sequential Process ◽  
Insulin Resistant ◽  
Sensitive Organ ◽  
And Function

Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors. Disrupted cardiac insulin signalling contributes to cardiac insulin resistance. Intrauterine under- or overnutrition alters offspring cardiac structure and function, notably cardiac hypertrophy, systolic and diastolic dysfunction, and hypertension that precede the onset of cardiovascular disease. Optimal intrauterine nutrition and oxygen saturation are required for normal cardiac development in offspring and the maintenance of their cardiovascular physiology.

scholarly journals Novel Insights From Human Studies on the Role of High-Density Lipoprotein in Mortality and Noncardiovascular Disease

2020 ◽  
Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Therapeutic Potential ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Cancer Type ◽  
Health And Disease ◽  
And Function

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.

scholarly journals EARLY TIME RESTRICTED FEEDING IMPROVES HIGH DENSITY LIPOPROTEIN FUNCTION IN GERIATRIC MONKEYS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S104-S104
Author(s):  
Kylie Kavanagh ◽  
Alexander Bashore ◽  
Matthew Davis ◽  
Chrissy Sherrill ◽  
John Parks
Keyword(s):  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Plasma Cholesterol ◽  
Biological Effects ◽  
Density Lipoprotein ◽  
Early Time ◽  
High Density ◽  
Vervet Monkeys ◽  
Restricted Feeding ◽  
Hdl Function

Abstract Ageing conveys the greatest risk for cardiovascular disease (CVD) development, which is the dominant cause of mortality in developed nations. High density lipoprotein (HDL) particles mediate reverse cholesterol transport, are anti-inflammatory and their function predicts CVD. We observed lower plasma cholesterol efflux capacity in geriatric vervet monkeys (p=0.03) when consuming either healthy or Western diets. Adult (n=16) and geriatric (n=19) monkeys were stratified into groups fed Western diet on ad libitum (Ad Lib) or early time restricted feeding (eTFR) schedules. eTRF supplied excess food only between 6am to 2pm. Housing, seasonality and fasting conditions for data and sample collections were equivalent. After 6 months, cholesterol efflux to HDL was greater in eTRF monkeys (p=0.01), with no age by group interaction. Efflux media and plasma was chromatographically separated to confirm labelled cholesterol, and enzymatically measured cholesterol, respectively, was affiliated with HDL particles. eTRF monkeys had higher total plasma cholesterol levels (p=0.03) which was due to greater cholesterol amounts associated with only HDL, and resulted in HDL particles that were larger. eTRF resulted in robustly better HDL function such that measures from geriatric individuals were comparable to younger adults. Additionally, no differences in adiposity was observed in eTRF monkeys. Few interventions are known to raise HDL levels, and more importantly, are confirmed to improve HDL function. Our study is to date the largest, longest, controlled eTRF evaluation in primates and we show that positive biological effects are observable in HDL isolated from both adult and geriatric individuals independently of weight change.

scholarly journals The Role of level and function of High Density Lipoprotein (HDL) in Cardiovascular Diseases

2020 ◽  
pp. 118-127
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Inverse Relationship ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
High Density ◽  
Peripheral Tissues ◽  
Hdl Function

High-density lipoprotein (HDL) is a set of particles with heterogeneous structures that have different functions due to various compounds including surface charge, size, lipid, and protein compounds. Several prospective epidemiological studies have demonstrated that there is a clear inverse relationship between serum HDL concentration and risk of coronary heart disease, despite this relationship, clinical evidence has only challenged the usefulness of higher levels of HDL-C in predicting the risk of cardiovascular diseases (CVD) and have proven that the structure of HDL is altered and loosed function. Therefore, extensive research is needed to identify new agents and biomarkers to improve HDL function and reduce the risk of cardiovascular disease. Given that the most important function of HDL is to transfer excess cholesterol from peripheral tissues and macrophage cells through a receptor called ABCA1 and direct it to the liver, plays an important role in protecting the formation of atherosclerotic plaque. This molecule can provide a strong protective effect against oxidative damage caused by free radicals with intermittent inhibition of the production of pro-inflammatory oxidized lipids in the intima layer of arteries. There is an inverse relationship between the ability to efflux cholesterol and the prevalence of CVD. The ability to remove cholesterol from macrophages by HDL, it is a crucial criterion for determining HDL performance, and it has a strong inverse relationship with carotid intima-media thickness and coronary artery stenosis in angiography independent of HDL level. Key Words: High Density Lipoprotein; Cardiovascular Disease; Atherosclerosis; Lipoprotein

scholarly journals HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition

2020 ◽  
Author(s):  
Samar R. El Khoudary ◽  
Xirun Chen ◽  
Alexis Nasr ◽  
Jeff Billheimer ◽  
Maria Mori Brooks ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipid Content ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Menstrual Period ◽  
Resonance Spectroscopy ◽  
Hdl Function ◽  
Menopause Transition ◽  
And Function

Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

scholarly journals Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function

2020 ◽  
Vol 21 (23) ◽  
pp. 8985
Author(s):  
Julia T. Stadler ◽  
Gunther Marsche
Keyword(s):  
High Density Lipoprotein ◽  
Virgin Olive Oil ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherogenic Dyslipidemia ◽  
Hdl Function ◽  
Increased Risk ◽  
And Function ◽  
The Impact

In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate. Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.

scholarly journals Diabetes and atherothrombosis: The circadian rhythm and role of melatonin in vascular protection

2020 ◽  
Vol 17 (3) ◽  
pp. 147916412092058
Author(s):  
Anastasia Otamas ◽  
Peter J Grant ◽  
Ramzi A Ajjan
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Circadian Rhythm ◽  
Large Scale ◽  
Coagulation Factors ◽  
Coagulation Cascade ◽  
Current Evidence ◽  
Low Grade ◽  
Vascular Protection ◽  
Increased Risk

Obesity-related euglycaemic insulin resistance clusters with cardiometabolic risk factors, contributing to the development of both type 2 diabetes and cardiovascular disease. An increased thrombotic tendency in diabetes stems from platelet hyperactivity, enhanced activity of prothrombotic coagulation factors and impaired fibrinolysis. Furthermore, a low-grade inflammatory response and increased oxidative stress accelerate the atherosclerotic process and, together with an enhanced thrombotic environment, result in premature and more severe cardiovascular disease. The disruption of circadian cycles in man secondary to chronic obesity and loss of circadian cues is implicated in the increased risk of developing diabetes and cardiovascular disease. Levels of melatonin, the endogenous synchronizer of circadian rhythm, are reduced in individuals with vascular disease and those with deranged glucose metabolism. The anti-inflammatory, antihypertensive, antioxidative and antithrombotic activities of melatonin make it a potential therapeutic agent to reduce the risk of vascular occlusive disease in diabetes. The mechanisms behind melatonin-associated reduction in procoagulant response are not fully known. Current evidence suggests that melatonin inhibits platelet aggregation and might affect the coagulation cascade, altering fibrin clot structure and/or resistance to fibrinolysis. Large-scale clinical trials are warranted to investigate the effects of modulating the circadian clock on insulin resistance, glycaemia and cardiovascular outcome.

scholarly journals The role of level and function of High Density Lipoprotein (HDL) in Cardiovascular Diseases

2020 ◽  
pp. 118-127
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Inverse Relationship ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
High Density ◽  
Key Words Atherosclerosis ◽  
Peripheral Tissues ◽  
Hdl Function

High-density lipoprotein (HDL) is a set of particles with heterogeneous structures that have different functions due to various compounds including surface charge, size, lipid, and protein compounds. Several prospective epidemiological studies have demonstrated that there is a clear inverse relationship between serum HDL concentration and risk of coronary heart disease, despite this relationship, clinical evidence has only challenged the usefulness of higher levels of HDL-C in predicting the risk of cardiovascular diseases (CVD) and have proven that the structure of HDL is altered and loosed function. Therefore, extensive research is needed to identify new agents and biomarkers to improve HDL function and reduce the risk of cardiovascular disease. Given that the most important function of HDL is to transfer excess cholesterol from peripheral tissues and macrophage cells through a receptor called ABCA1 and direct it to the liver, plays an important role in protecting the formation of atherosclerotic plaque. This molecule can provide a strong protective effect against oxidative damage caused by free radicals with intermittent inhibition of the production of pro-inflammatory oxidized lipids in the intima layer of arteries. There is an inverse relationship between the ability to efflux cholesterol and the prevalence of CVD. The ability to remove cholesterol from macrophages by HDL, it is a crucial criterion for determining HDL performance, and it has a strong inverse relationship with carotid intima-media thickness and coronary artery stenosis in angiography independent of HDL level. Key Words: Atherosclerosis; Cardiovascular Disease; High Density Lipoprotein; Lipoprotein

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