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Oxidative Medicine and Cellular... 2020Dyslipidaemia has a prominent role in the onset of notorious atherosclerosis, a disease of medium to large arteries. Atherosclerosis is the prime root of cardiovascular... (Review)
Review
Dyslipidaemia has a prominent role in the onset of notorious atherosclerosis, a disease of medium to large arteries. Atherosclerosis is the prime root of cardiovascular events contributing to the most considerable number of morbidity and mortality worldwide. Factors like cellular senescence, genetics, clonal haematopoiesis, sedentary lifestyle-induced obesity, or diabetes mellitus upsurge the tendency of atherosclerosis and are foremost pioneers to definitive transience. Accumulation of oxidized low-density lipoproteins (Ox-LDLs) in the tunica intima triggers the onset of this disease. In the later period of progression, the build-up plaques rupture ensuing thrombosis (completely blocking the blood flow), causing myocardial infarction, stroke, and heart attack, all of which are common atherosclerotic cardiovascular events today. The underlying mechanism is very well elucidated in literature but the therapeutic measures remains to be unleashed. Researchers tussle to demonstrate a clear understanding of treating mechanisms. A century of research suggests that lowering LDL, statin-mediated treatment, HDL, and lipid-profile management should be of prime interest to retard atherosclerosis-induced deaths. We shall brief the Ox-LDL-induced atherogenic mechanism and the treating measures in line to impede the development and progression of atherosclerosis.
Topics: Antioxidants; Atherosclerosis; Endothelium; Humans; Lipoproteins, LDL; Macrophages; Oxidative Stress; Reactive Oxygen Species; Risk Factors
PubMed: 33014272
DOI: 10.1155/2020/5245308 -
Cardiovascular Research Feb 2022The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow's triad of hypercoagulability, structural... (Review)
Review
The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow's triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis.
Topics: Atrial Fibrillation; Cholesterol, LDL; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Thrombosis
PubMed: 33483737
DOI: 10.1093/cvr/cvab017 -
Trends in Cardiovascular Medicine Jan 2019We provide an up-to-date overview of current topics surrounding oxidized low-density lipoprotein (oxLDL) and its related antibodies in the quest to better identify the... (Review)
Review
We provide an up-to-date overview of current topics surrounding oxidized low-density lipoprotein (oxLDL) and its related antibodies in the quest to better identify the individuals at risk of cardiovascular disease and atherosclerotic plaques with unfavorable characteristics. We discuss the potential of oxLDL and anti-oxLDL antibodies as serum biomarkers of cardiovascular disease and emerging studies examining the targeting of arterial oxLDL for imaging and therapeutic delivery.
Topics: Animals; Antibodies; Arteries; Atherosclerosis; Biomarkers; Humans; Immunization; Lipoproteins, LDL; Molecular Imaging; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Vaccines
PubMed: 29934015
DOI: 10.1016/j.tcm.2018.05.010 -
Drug Delivery Dec 2021Native nanostructured lipoproteins such as low- and high-density lipoproteins (LDL and HDL) are powerful tools for the targeted delivery of drugs and imaging agents.... (Review)
Review
Native nanostructured lipoproteins such as low- and high-density lipoproteins (LDL and HDL) are powerful tools for the targeted delivery of drugs and imaging agents. While the cellular recognition of well-known HDL-based carriers occurs via interactions with an HDL receptor, the selective delivery and uptake of LDL particles by target cells are more complex. The most well-known mode of LDL-based delivery is via the interaction between apolipoprotein B (Apo-B) - the main protein of LDL - and the low-density lipoprotein receptor (LDLR). LDLR is expressed in the liver, adipocytes, and macrophages, and thus selectively delivers LDL carriers to these cells and tissues. Moreover, the elevated expression of LDLR in tumor cells indicates a role for LDL in the targeted delivery of chemotherapy drugs. In addition, chronic inflammation associated with hypercholesterolemia (i.e., high levels of endogenous LDL) can be abated by LDL carriers, which outcompete the deleterious oxidized LDL for uptake by macrophages. In this case, synthetic LDL nanocarriers act as 'eat-me' signals and exploit mechanisms of native LDL uptake for targeted drug delivery and imaging. Lastly, recent studies have shown that the delivery of LDL-based nanocarriers to macrophages via fluid-phase pinocytosis is a promising tool for atherosclerosis imaging. Hence, the present review summarizes the use of natural and synthetic LDL-based carriers for drug delivery and imaging and discusses various mechanisms of targeting.
Topics: Animals; Atherosclerosis; Drug Carriers; Humans; Hypercholesterolemia; Lipoproteins, HDL; Lipoproteins, LDL; Macrophages; Nanomedicine; Receptors, Lipoprotein
PubMed: 33594923
DOI: 10.1080/10717544.2021.1886199 -
Free Radical Biology & Medicine Oct 2017Based on the significance of oxidized low-density lipoprotein (LDL) in health and disease, this review focuses on human studies addressing oxidation of LDL, including... (Review)
Review
Based on the significance of oxidized low-density lipoprotein (LDL) in health and disease, this review focuses on human studies addressing oxidation of LDL, including three lines of biomarkers, (i) ex vivo LDL resistance to oxidation, a "challenge test" model, (ii) circulating oxidized LDL, indicating the "current in vivo status", and (iii) autoantibodies against oxidized LDL as fingerprints of an immune response to oxidized LDL, along with circulating oxysterols and 4-hydroxynonenal as biomarkers of lipid peroxidation. Lipid peroxidation and oxidized LDL are hallmarks in the development of various metabolic, cardiovascular and other diseases. Changes further occur across life stages from infancy to older age as well as in athletes and smokers. Given their responsiveness to targeted nutritional interventions, markers of LDL oxidation have been employed in a rapidly growing number of human studies for more than 2 decades. There is growing interest in foods, which, besides providing energy and nutrients, exert beneficial effects on human health, such as protection of DNA, proteins and lipids from oxidative damage. Any health claim, however, needs to be substantiated by supportive evidence derived from human studies, using reliable biomarkers to demonstrate such beneficial effects. A large body of evidence has accumulated, demonstrating protection of LDL from oxidation by bioactive food compounds, including vitamins, other micronutrients and secondary plant ingredients, which will facilitate the selection of oxidation biomarkers for future human intervention studies and health claim support.
Topics: Aldehydes; Animals; Autoantibodies; Biomarkers; Cardiovascular Diseases; Clinical Trials as Topic; Fish Oils; Functional Food; Humans; Lipid Peroxidation; Lipoproteins, LDL; Oxysterols
PubMed: 28456641
DOI: 10.1016/j.freeradbiomed.2017.04.345 -
Advances in Clinical and Experimental... Apr 2019Chemotherapy for colorectal cancer remains an unsatisfactory method of treatment and requires the development of more advanced drug delivery systems (DDSs). Among...
BACKGROUND
Chemotherapy for colorectal cancer remains an unsatisfactory method of treatment and requires the development of more advanced drug delivery systems (DDSs). Among inorganic materials, silica nanoparticles (SLNs) have been considered a suitable candidate to be developed as versatile carriers for drug delivery and imaging applications. Low-density lipoprotein (LDL) is a widespread material that is responsible for cholesterol transport in plasma. The concept of employing LDL-modified nanoparticles for tumor-targeted drug delivery has been widely adopted.
OBJECTIVES
The objective of this study was to develop and test a new DDS for effective chemotherapy of colorectal cancer.
MATERIAL AND METHODS
We successfully developed an Adriamycin (Adr)-loaded DDS based on LDL-modified SLNs (LDL/SLN/Adr). The tumor-homing property of LDL and the drug-loading capability of SLNs were combined to prepare LDL/SLN/Adr that can specifically deliver Adr to the cancer site to achieve effective chemotherapy of HT-29 colorectal cancer.
RESULTS
In vitro analysis showed that LDL/SLN/Adr consisted of nano-sized particles and was capable of targeting the low-density lipoprotein receptors (LDLR) which were overexpressed in many cancer cell lines. As a result, LDL/SLN/Adr exerted better cytotoxicity than unmodified SLNs and free drugs. In vivo imaging and anticancer assays also confirmed the preferable tumor-homing and enhanced anticancer effect of LDL/SLN/Adr.
CONCLUSIONS
LDL/SLN/Adr might be a promising DDS for effective chemotherapy of colorectal cancer.
Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; Colorectal Neoplasms; Doxorubicin; Drug Carriers; Drug Delivery Systems; Hep G2 Cells; Humans; Lipoproteins, LDL; Nanoparticles; Silicon Dioxide
PubMed: 30070081
DOI: 10.17219/acem/79561 -
Bioengineered Mar 2022Atherosclerosis (AS) is a life-threatening cardiovascular disease and it has been reported that endothelial dysfunction is the initial inducer of AS. Recent reports...
Atherosclerosis (AS) is a life-threatening cardiovascular disease and it has been reported that endothelial dysfunction is the initial inducer of AS. Recent reports suggest that inflammation and oxidative stress-induced cell senescence are main inducers of endothelial dysfunction. Nintedanib is an effective inhibitor of multityrosine kinase receptors developed for the treatment of fibrosis, which was recently reported to exert inhibitory effects against inflammation and oxidative stress. The present study plans to study the effect and mechanism of Nintedanib on endothelial dysfunction. We found that in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs), the increased production of total cholesterol (TC), free cholesterol (FC), and pro-inflammatory cytokines were observed, reversed by 10 μM and 25 μM Nintedanib. The elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as the declined activity of glutathione peroxidase (GSH-Px) in ox-LDL-treated HUVECs, were significantly abolished by 10 μM and 25 μM Nintedanib. Increased proportion of senescence-associated β-galactosidase (SA-β-gal) positive staining cells, activated p53/p21 pathway, and promoted cell fraction in the G0/G1 phase were observed in ox-LDL-treated HUVECs, all of which were dramatically reversed by 10 μM and 25 μM Nintedanib. Lastly, the increased expression level of Arginase-II (Arg-II) in HUVECs by ox-LDL was repressed by Nintedanib. The protective effects of Nintedanib on ox-LDL- induced cellular senescence were pronouncedly blocked by the overexpression of Arg-II. Collectively, our data suggest that Nintedanib mitigates ox-LDL-induced inflammation and cellular senescence in vascular endothelial cells by downregulating Arg-II.
Topics: Apoptosis; Atherosclerosis; Cellular Senescence; Human Umbilical Vein Endothelial Cells; Humans; Indoles; Inflammation; Lipoproteins, LDL; Oxidative Stress
PubMed: 35236245
DOI: 10.1080/21655979.2022.2036913 -
Chemical Society Reviews Dec 2017Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery... (Review)
Review
Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery of theranostic agents. In contrast to the synthetic systems, LDL particles are intrinsically biocompatible and biodegradable, together with reduced immunogenicity and natural capabilities to target cancerous cells and to escape from the recognition and elimination by the reticuloendothelial system. Enticed by these attributes, a number of strategies have been developed for reconstituting LDL particles, including conjugation to the apolipoprotein, insertion into the phospholipid layer, and loading into the core. Here we present a tutorial review on the development of reconstituted LDL (rLDL) particles for theranostic applications. We start with a brief introduction to LDL and LDL receptor, as well as the advantages of using rLDL particles as a natural and versatile platform for the targeted delivery of theranostic agents. After a discussion of commonly used strategies for the reconstitution of LDL, we highlight the applications of rLDL particles in the staging of disease progression, treatment of lesioned tissues, and delivery of photosensitizers for photodynamic cancer therapy. We finish this review with a perspective on the remaining challenges and future directions.
Topics: Animals; Biomimetics; Drug Delivery Systems; Humans; Lipoproteins, LDL; Theranostic Nanomedicine
PubMed: 29104991
DOI: 10.1039/c7cs00492c -
Atherosclerosis Apr 2011Oxidative modifications in lipoproteins (LP), especially in low-density lipoproteins (LDL), are associated with initiation and progression of atherosclerosis. The levels... (Review)
Review
Oxidative modifications in lipoproteins (LP), especially in low-density lipoproteins (LDL), are associated with initiation and progression of atherosclerosis. The levels of a sub-fraction of LDL with oxidative characteristics, named electronegative LDL [LDL(-)], minimally oxidized LDL, and minus LDL, are known to be increased in subjects with familial hypercholesterolemia, hypertriglyceridemia, nonalcoholic steatohepatitis, diabetes mellitus, coronary artery disease, patients undergoing hemodialysis, and athletes after aerobic exercise. In addition to the oxidative profile, physical and biological characteristics of LDL(-) consist of nonenzymatic glycosylation, increased expression and activity of platelet-activating factor acetylhydrolase (PAF-AH) and phospholipase A(2) (PLA(2)), enriched NEFA content, hemoglobin and ApoB-100 cross-linking, and increase in ApoC-III and ApoE in LDL. Herein, we summarize the state of the art of the up-to-date body of knowledge on the possible origin and impact of LDL(-) in health and disease. Further, the potential perspectives of using LDL(-) as a biomarker in conditions under metabolic stress are also discussed.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Apolipoprotein B-100; Apolipoprotein C-III; Apolipoproteins E; Humans; Lipoproteins, LDL; Oxidation-Reduction
PubMed: 21292266
DOI: 10.1016/j.atherosclerosis.2010.12.028 -
Lipids in Health and Disease Jun 2019Breast cancer is a heterogeneous disease with increasing incidence and mortality and represents one of the most common cancer types worldwide. Low-density lipoprotein... (Review)
Review
Breast cancer is a heterogeneous disease with increasing incidence and mortality and represents one of the most common cancer types worldwide. Low-density lipoprotein (LDL) is a complex particle composed of several proteins and lipids, which carries cholesterol into peripheral tissues and also affects the metabolism of fatty acids. Recent reports have indicated an emerging role of LDL in breast cancer, affecting cell proliferation and migration, thereby facilitating disease progression. However, controversy still exists among distinct types of breast cancer that can be affected by LDL. Classical therapeutic approaches, such as radiotherapy, chemotherapy, and lipid-lowering drugs were also reported as affecting LDL metabolism and content in breast cancer patients. Therefore, in this review we summarized and discussed the role of LDL in the development and treatment of breast cancer.
Topics: Breast Neoplasms; Cell Line, Tumor; Fatty Acids, Unsaturated; Female; Humans; Lipid Metabolism; Lipoproteins, LDL; Prognosis
PubMed: 31182104
DOI: 10.1186/s12944-019-1075-7