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1.
Emerging roles for high-density lipoproteins in neurodegenerative disorders.
Bahrami, A, Barreto, GE, Lombardi, G, Pirro, M, Sahebkar, A
BioFactors (Oxford, England). 2019;(5):725-739
Abstract
Lipoproteins are the complexes of different lipids and proteins, which are devoted to the transport and clearance of lipids or lipid-related molecules in the circulation. Lipoproteins have been found to play a crucial role in brain function and may influence myelination process. Among lipoproteins, high-density lipoproteins (HDLs) and their major protein component, apoA-I, are directly involved in cholesterol efflux in the brain. It has been suggested that inadequate or dysfunctional brain HDLs may contribute to cerebrovascular dysfunctions, neurodegeneration, or neurovascular instability. HDL deficiency could also promote cognitive decline through impacting on atherosclerotic risk. The focus of this review is to discuss knowledge on HDL dysregulation in neurological disorders. A better understanding on how changes in cellular HDL and apolipoprotein homeostasis affect central nervous system function may provide promising novel avenues for the treatment of specific HDL-related neurological disorders.
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2.
Low high-density lipoprotein and psychopathology: A review.
Douglas, J, Nasrallah, HA
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists. 2019;(3):209-213
Abstract
BACKGROUND An association between the level of total cholesterol and psychopathology has been the focus of numerous studies. Low total cholesterol has been found to be related to depression, personality disorders, and dissociative disorder. High cholesterol has been associated with schizophrenia, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder, and posttraumatic stress disorder. However, no reviews of the psychiatric correlates of high-density lipoprotein (HDL) have been published. We reviewed the literature for studies reporting a significant association between low or high levels of HDL and psychopathology. METHODS A search of major databases (PubMed and CINAHL) was conducted using the following keywords: HDL, depression, anxiety, schizophrenia, OCD, and psychiatric disorders. RESULTS Eight studies met our search criteria. Six of the 8 studies reported significantly higher rates of depression, anxiety, suicide attempts, and violent behaviors in participants with low HDL. CONCLUSIONS Overall, a low HDL may not only be associated with risk for cardiac disease, but also with increased risk for serious psychiatric disorders. Further controlled studies are warranted.
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3.
Humoral Immunity Against HDL Particle: A New Perspective in Cardiovascular Diseases?
Satta, N, Frias, MA, Vuilleumier, N, Pagano, S
Current pharmaceutical design. 2019;(29):3128-3146
Abstract
BACKGROUND Autoimmune diseases are closely associated with cardiovascular diseases (CVD). Over the last decades, the comprehension of atherosclerosis, the principal initiator of CVD, evolved from a lipidcentered disease to a predominant inflammatory and immune response-driven disease displaying features of autoimmunity against a broad range of auto-antigens, including lipoproteins. Among them, high density lipoproteins (HDL) are important actors of cholesterol transport and bear several anti-atherogenic properties, raising a growing interest as therapeutic targets to decrease atherosclerosis and CVD burden, with nevertheless rather disappointing results so far. Reflecting HDL composition complexity, autoimmune responses and autoantibodies against various HDL components have been reported. RESULTS In this review, we addressed the important complexity of humoral autoimmunity towards HDL and particularly how this autoimmune response could help improving our understanding of HDL biological implication in atherosclerosis and CVD. We also discussed several issues related to specific HDL autoantibody subclasses characteristics, including etiology, prognosis and pathological mechanisms according to Rose criteria. CONCLUSION Finally, we addressed the possible clinical value of using these antibodies not only as potential biomarkers of atherogenesis and CVD, but also as a factor potentially mitigating the benefit of HDL-raising therapies.
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4.
Dysfunctional HDL as a Therapeutic Target for Atherosclerosis Prevention.
Ossoli, A, Pavanello, C, Giorgio, E, Calabresi, L, Gomaraschi, M
Current medicinal chemistry. 2019;(9):1610-1630
Abstract
Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis. Among the various lipoprotein classes, however, high density lipoproteins (HDL) are inversely associated with the incidence of atherosclerosis, since they are able to exert a series of atheroprotective functions. The central role of HDL within the reverse cholesterol transport, their antioxidant and anti-inflammatory properties and their ability to preserve endothelial homeostasis are likely responsible for HDL-mediated atheroprotection. However, drugs that effectively raise HDL-C failed to result in a decreased incidence of cardiovascular event, suggesting that plasma levels of HDL-C and HDL function are not always related. Several evidences are showing that different pathologic conditions, especially those associated with an inflammatory response, can cause dramatic alterations of HDL protein and lipid cargo resulting in HDL dysfunction. Established and investigational drugs designed to affect lipid metabolism and to increase HDL-C are only partly effective in correcting HDL dysfunction.
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5.
ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity.
Babashamsi, MM, Koukhaloo, SZ, Halalkhor, S, Salimi, A, Babashamsi, M
Diabetes & metabolic syndrome. 2019;(2):1529-1534
Abstract
ATP-binding cassette transporter A1 (ABCA1) is an integral cell-membrane protein that mediates the rate-limiting step of high density lipoprotein (HDL) biogenesis and suppression of inflammation by triggering a number of signaling pathways via interacting with an apolipoprotein acceptor. The hepatic ABCA1 is involved in regulation of very low density lipoprotein (VLDL) production by affecting the apolipoprotein B trafficking and lipidation of VLDL particles. This protein is involved in protecting the function of pancreatic β-cells and insulin secretion by cholesterol homeostasis. Adipose tissue lipolysis is associated with ABCA1 activity. This transporter is involved in controlling obesity and insulin sensitivity by regulating triglyceride (TG) lipolysis and influencing on adiponectin, visfatin, leptin, and GLUT4 genes expression. The ABCA1 of skeletal muscle cells play a role in increasing the glucose uptake by enhancing the Akt phosphorylation and transferring GLUT4 to the plasma membrane. Abnormal status of ABCA1-regulated phenotypes is observed in metabolic syndrome. This syndrome is associated with the occurrence of many diseases. This review is a summary of the role of ABCA1 in HDL and VLDL production, homeostasis of insulin and glucose, suppression of inflammation and obesity controlling to provide a better insight into the association of this protein with metabolic syndrome.
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6.
High-Density Lipoprotein Subspecies in Health and Human Disease: Focus on Type 2 Diabetes.
Davidson, WS, Shah, AS
Methodist DeBakey cardiovascular journal. 2019;(1):55-61
Abstract
Plasma cholesterol levels of high-density lipoproteins (HDL) have been associated with cardioprotection for decades. However, there is an evolving appreciation that this lipoprotein class is highly heterogeneous with regard to composition and functionality. With the advent of advanced lipid-testing techniques and methods that allow both the quantitation and recovery of individual particle populations, we are beginning to connect the functionality of HDL subspecies with chronic metabolic diseases. In this review, we examine type 2 diabetes (T2D) and explore our current understanding of how obesity, insulin resistance, and hyperglycemia affect, and may be affected by, HDL subspeciation. We discuss mechanistic aspects of how insulin resistance may alter lipoprotein profiles and how this may impact the ability of HDL to mitigate both atherosclerotic disease and diabetes itself. Finally, we call for more detailed studies examining the impact of T2D on specific HDL subspecies and their functions. If these particles can be isolated and their compositions and functions fully elucidated, it may become possible to manipulate the levels of these specific particles or target the protective functions to reduce the incidence of coronary heart disease.
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7.
High-Density Lipoprotein Components and Functionality in Cancer: State-of-the-Art.
Ganjali, S, Ricciuti, B, Pirro, M, Butler, AE, Atkin, SL, Banach, M, Sahebkar, A
Trends in endocrinology and metabolism: TEM. 2019;(1):12-24
Abstract
Cancer is the second leading cause of death in western countries, and thus represents a major global public health issue. Whilst it is well-recognized that diet, obesity, and smoking are risk factors for cancer, the role of low levels of high-density lipoprotein cholesterol (HDL-C) in cancer is less well appreciated. Conflicting evidence suggests that serum HDL-C levels may be either positively or negatively associated with cancer incidence and mortality. Such disparate associations are supported in part by the multitude of high-density lipoprotein (HDL) functions that can all have an impact on cancer cell biology. The aim of this review is to provide a comprehensive overview of the crosstalk between HDLs and cancer, focusing on the molecular mechanisms underlying this association.
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8.
Incretins and Lipid Metabolism.
Tsimihodimos, V, Elisaf, M
Current medicinal chemistry. 2018;(18):2133-2139
Abstract
BACKGROUND Recent findings indicate that incretin hormones and incretin-based therapies may affect the metabolism of lipoproteins, although the corresponding mechanisms are not clearly defined. OBJECTIVE To summarize the available data on the mechanisms linking incretins with the characteristics of serum lipoproteins and discuss the clinical implications of these relationships. METHODS PubMed was searched using the terms "incretins", "GLP-1", "GIP" and "lipids", "dyslipidemia", "triglycerides", "apolipoprotein B48". All articles published in the English language until June 2016 were assessed and the relevant information is presented here. RESULTS GLP-1, and therapies that increase its activity, exert a beneficial effect on lipoprotein metabolism that is translated in a reduction in the fasting and postprandial concentration of triglycerides and a small improvement in the concentration and function of HDLs. In addition, a shift towards larger, less atherogenic particles usually follows the administration of GLP-1 receptor agonists. The mechanisms that underlie these changes involve a direct effect of GLP- 1 on the hepatic and intestinal production of triglyceride-rich lipoproteins, the GLP-1 induced increase in the production and function of insulin, the activation of specific areas of central nervous system as well as the increase in the peripheral utilization of triglycerides for energy production. On the other hand, GLP-2 increases the absorption of dietary fat and the production of triglyceride-rich lipoproteins while the role of GIP on lipid metabolism remains indeterminate. CONCLUSION GLP-1 and incretin-based therapies favorably affect lipid metabolism. These effects may contribute to the beneficial effects of incretin-based therapies on atherosclerosis and fatty liver disease.
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9.
JCL roundtable: High-density lipoprotein function and reverse cholesterol transport.
Cuchel, M, Rohatgi, A, Sacks, FM, Guyton, JR
Journal of clinical lipidology. 2018;(5):1086-1094
Abstract
High-density lipoproteins (HDL) have been known since the 1960s to be associated with protection from atherosclerotic cardiovascular disease. However, the mechanisms of this protection are unclear. The extent to which HDL per se vs other correlated metabolic factors may mitigate atherosclerosis has been seriously questioned. In fact, new epidemiologic studies have found that in some clinical settings, very high HDL cholesterol levels correlate with increased atherosclerotic risk. Most importantly, over the past 2 decades, randomized clinical trials targeting HDL have failed to reproduce the usual epidemiologic inverse relation of HDL cholesterol to atherosclerotic events. In this roundtable discussion, we bring together 3 expert investigators working in the HDL field to elucidate questions of HDL function. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. ApoA-I is the major functional apoprotein of HDL, but apoE- and apoC-III-containing subpopulations of HDL may have significant roles. Anti- and pro-inflammatory functions of various HDL particles, as well as the role of oxidative and other modifications, are gaining attention.
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10.
High-Density Lipoproteins: Effects on Vascular Function and Role in the Immune Response.
Haghikia, A, Landmesser, U
Cardiology clinics. 2018;(2):317-327
Abstract
The focus in studies of high-density lipoproteins was on their capacity to remove excess cholesterol and deliver it to the liver. Other functions and vascular effects have been described. Clinical trials and translational/genetic studies have led to a refined understanding of the role of high-density lipoprotein; it is likely not a causal cardiovascular risk factor. In healthy subjects, it limits lipid oxidation, protects endothelial cell functions/integrity, and exerts antiinflammatory/antiapoptotic effects. In patients with coronary disease or diabetes, it undergoes modifications/remodeling, resulting in dysfunctional high-density lipoprotein. We summarize recent findings about the regulation of its function and discuss the clinical implications.