International Journal of Molecular Sciences

Editorial

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Open AccessEditorial

Lipidomics: An Evolving Discipline in Molecular Sciences

by Giuseppe Astarita and Mario Ollero

Int. J. Mol. Sci. 2015, 16(4), 7748-7752; https://doi.org/10.3390/ijms16047748 - 8 Apr 2015

Cited by 6 | Viewed by 4815

Abstract

Recent advances in technologies for lipid analysis have contributed to the consolidation of lipidomics as a distinct discipline in molecular sciences [1–6]. [...] Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

Research

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A Simple and Effective Mass Spectrometric Approach to Identify the Adulteration of the Mediterranean Diet Component Extra-Virgin Olive Oil with Corn Oil

by Francesco Di Girolamo, Andrea Masotti, Isabella Lante, Margherita Scapaticci, Cosima Damiana Calvano, Carlo Zambonin, Maurizio Muraca and Lorenza Putignani

Int. J. Mol. Sci. 2015, 16(9), 20896-20912; https://doi.org/10.3390/ijms160920896 - 1 Sep 2015

Cited by 26 | Viewed by 6014

Abstract

Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest [...] Read more.

Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest source of agricultural fraud in the European Union, with important health implications for consumers, mainly due to the introduction of seed oil-derived allergens causing, especially in children, severe food allergy phenomena. In this regard, revealing adulterations of EVOO is of fundamental importance for health care and prevention reasons, especially in children. To this aim, effective analytical methods to assess EVOO purity are necessary. Here, we propose a simple, rapid, robust and very sensitive method for non-specialized mass spectrometric laboratory, based on the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) coupled to unsupervised hierarchical clustering (UHC), principal component (PCA) and Pearson’s correlation analyses, to reveal corn oil (CO) adulterations in EVOO at very low levels (down to 0.5%). Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1951 KiB

Open AccessArticle

Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

by Mariateresa Maldini, Fausta Natella, Simona Baima, Giorgio Morelli, Cristina Scaccini, James Langridge and Giuseppe Astarita

Int. J. Mol. Sci. 2015, 16(6), 13678-13691; https://doi.org/10.3390/ijms160613678 - 15 Jun 2015

Cited by 24 | Viewed by 7139

Abstract

The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach [...] Read more.

The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower) is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle). We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the potential of an unbiased omics approach for the comprehensive study of the metabolism. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1030 KiB

Open AccessArticle

Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

by Sarah A. Brigandi, Hong Shao, Steven Y. Qian, Yiping Shen, Bai-Lin Wu and Jing X. Kang

Int. J. Mol. Sci. 2015, 16(5), 10061-10076; https://doi.org/10.3390/ijms160510061 - 4 May 2015

Cited by 78 | Viewed by 12792

Abstract

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid [...] Read more.

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1907 KiB

Open AccessArticle

Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits

by Lazar A. Bojic, David G. McLaren, Vinit Shah, Stephen F. Previs, Douglas G. Johns and Jose M. Castro-Perez

Int. J. Mol. Sci. 2014, 15(12), 23283-23293; https://doi.org/10.3390/ijms151223283 - 15 Dec 2014

Cited by 16 | Viewed by 6164

Abstract

The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework [...] Read more.

The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1707 KiB

Open AccessArticle

Interactions of Borneol with DPPC Phospholipid Membranes: A Molecular Dynamics Simulation Study

by Qianqian Yin, Xinyuan Shi, Haiou Ding, Xingxing Dai, Guang Wan and Yanjiang Qiao

Int. J. Mol. Sci. 2014, 15(11), 20365-20381; https://doi.org/10.3390/ijms151120365 - 6 Nov 2014

Cited by 19 | Viewed by 8131

Abstract

Borneol, known as a “guide” drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol’s penetration enhancing effect, the molecular basis of its action on bio-membranes is [...] Read more.

Borneol, known as a “guide” drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol’s penetration enhancing effect, the molecular basis of its action on bio-membranes is still unclear. We carried out a series of coarse-grained molecular dynamics simulations with the borneol concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis) to study the interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3-phosphatidylcholine) bilayer membrane, and the temperature effects were also considered. At concentrations below 21.89%, borneol’s presence only caused DPPC bilayer thinning and an increase in fluidity; A rise in temperature could promote the diffusing progress of borneol. When the concentration was 21.89% or above, inverted micelle-like structures were formed within the bilayer interior, which led to increased bilayer thickness, and an optimum temperature was found for the interaction of borneol with the DPPC bilayer membrane. These findings revealed that the choice of optimal concentration and temperature is critical for a given application in which borneol is used as a penetration enhancer. Our results not only clarify some molecular basis for borneol’s penetration enhancing effects, but also provide some guidance for the development and applications of new preparations containing borneol. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1571 KiB

Open AccessArticle

Nuclear Lipid Microdomain as Resting Place of Dexamethasone to Impair Cell Proliferation

by Samuela Cataldi, Michela Codini, Giacomo Cascianelli, Sabina Tringali, Anna Rita Tringali, Andrea Lazzarini, Alessandro Floridi, Elisa Bartoccini, Mercedes Garcia-Gil, Remo Lazzarini, Francesco Saverio Ambesi-Impiombato, Francesco Curcio, Tommaso Beccari and Elisabetta Albi

Int. J. Mol. Sci. 2014, 15(11), 19832-19846; https://doi.org/10.3390/ijms151119832 - 31 Oct 2014

Cited by 12 | Viewed by 5705

Abstract

The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We [...] Read more.

The action of dexamethasone is initiated by, and strictly dependent upon, the interaction of the drug with its receptor followed by its translocation into the nucleus where modulates gene expression. Where the drug localizes at the intranuclear level is not yet known. We aimed to study the localization of the drug in nuclear lipid microdomains rich in sphingomyelin content that anchor active chromatin and act as platform for transcription modulation. The study was performed in non-Hodgkin’s T cell human lymphoblastic lymphoma (SUP-T1 cell line). We found that when dexamethasone enters into the nucleus it localizes in nuclear lipid microdomains where influences sphingomyelin metabolism. This is followed after 24 h by a cell cycle block accompanied by the up-regulation of cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 1B (CDKN1B), growth arrest and DNA-damage 45A (GADD45A), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes and by the reduction of signal transducer and activator of transcription 3 (STAT3) and phospho signal transducer and activator of transcription 3 (phoshoSTAT3) proteins. After 48 h some cells show morphological changes characteristic of apoptosis while the number of the cells that undergo cell division and express B-cell lymphoma-2 (Bcl-2) is very low. We suggest that the integrity of nuclear lipid microdomains is important for the response to glucocorticoids of cancer cells. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1453 KiB

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FT-IR Microspectrometry Reveals the Variation of Membrane Polarizability due to Epigenomic Effect on Epithelial Ovarian Cancer

by Morris M. H. Hsu, Pei-Yu Huang, Yao-Chang Lee, Yuang-Chuen Fang, Michael W. Y. Chan and Cheng-I Lee

Int. J. Mol. Sci. 2014, 15(10), 17963-17973; https://doi.org/10.3390/ijms151017963 - 8 Oct 2014

Cited by 10 | Viewed by 5932

Abstract

Ovarian cancer, as well as other cancers, is primarily caused by methylation at cytosines in CpG islands, but the current marker for ovarian cancer is low in sensitivity and failed in early-stage detection. Fourier transform infrared (FT-IR) spectroscopy is powerful in analysis of [...] Read more.

Ovarian cancer, as well as other cancers, is primarily caused by methylation at cytosines in CpG islands, but the current marker for ovarian cancer is low in sensitivity and failed in early-stage detection. Fourier transform infrared (FT-IR) spectroscopy is powerful in analysis of functional groups within molecules, and infrared microscopy illustrates the location of specific groups within single cells. In this study, we applied HPLC and FT-IR microspectrometry to study normal epithelial ovarian cell line immortalized ovarian surface epithelium (IOSE), two epithelial ovarian cell lines (A2780 and CP70) with distinct properties, and the effect of a cancer drug 5-aza-2'-deoxycytidine (5-aza) without labeling. Our results reveal that inhibition of methylation on cytosine with 5-aza initiates the protein expression. Furthermore, paraffin-adsorption kinetic study allows us to distinguish hypermethylated and hypomethyated cells, and this assay can be a potential diagnosis method for cancer screening. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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Impact of Inhaled Nitric Oxide on the Sulfatide Profile of Neonatal Rat Brain Studied by TOF-SIMS Imaging

by Hanane Kadar, Hoa Pham, David Touboul, Alain Brunelle and Olivier Baud

Int. J. Mol. Sci. 2014, 15(4), 5233-5245; https://doi.org/10.3390/ijms15045233 - 25 Mar 2014

Cited by 12 | Viewed by 7070

Abstract

Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated in [...] Read more.

Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated in preclinical models is inhaled nitric oxide (iNO). We have assessed the effect of this therapy on brain lipid content in air- and iNO-exposed rat pups by mass spectrometry imaging using a time-of-flight secondary ion mass spectrometry (TOF-SIMS) method. This technique was used to map the variations in lipid composition of the rat brain and, particularly, of the white matter. Triplicate analysis showed a significant increase of sulfatides (25%–50%) in the white matter on Day 10 of life in iNO-exposed animals from Day 0–7 of life. These robust, repeatable and semi-quantitative data demonstrate a potent effect of iNO at the molecular level. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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6976 KiB

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Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

by Li-Xia Feng, Min Li, Yong-Jun Liu, Shao-Mei Yang and Na Zhang

Int. J. Mol. Sci. 2014, 15(3), 4201-4220; https://doi.org/10.3390/ijms15034201 - 10 Mar 2014

Cited by 36 | Viewed by 7236

Abstract

Ceramide (CE)-based combination therapy (CE combination) as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX) (CE + DTX) [...] Read more.

Ceramide (CE)-based combination therapy (CE combination) as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX) (CE + DTX) and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and combination index (CI) assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31) and human breast carcinoma cell (MCF-7, CI = 0.48). The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01). The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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Review

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Lipidomics by Supercritical Fluid Chromatography

by Laurent Laboureur, Mario Ollero and David Touboul

Int. J. Mol. Sci. 2015, 16(6), 13868-13884; https://doi.org/10.3390/ijms160613868 - 17 Jun 2015

Cited by 95 | Viewed by 12524

Abstract

This review enlightens the role of supercritical fluid chromatography (SFC) in the field of lipid analysis. SFC has been popular in the late 1980s and 1990s before almost disappearing due to the commercial success of liquid chromatography (LC). It is only 20 years [...] Read more.

This review enlightens the role of supercritical fluid chromatography (SFC) in the field of lipid analysis. SFC has been popular in the late 1980s and 1990s before almost disappearing due to the commercial success of liquid chromatography (LC). It is only 20 years later that a regain of interest appeared when new commercial instruments were introduced. As SFC is fully compatible with the injection of extracts in pure organic solvent, this technique is perfectly suitable for lipid analysis and can be coupled with either highly universal (UV or evaporative light scattering) or highly specific (mass spectrometry) detection methods. A short history of the use of supercritical fluids as mobile phase for the separation oflipids will be introduced first. Then, the advantages and drawbacks of SFC are discussed for each class of lipids (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, prenols, polyketides) defined by the LIPID MAPS consortium. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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Open AccessReview

Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

by Anthony Arlia-Ciommo, Amanda Piano, Veronika Svistkova, Sadaf Mohtashami and Vladimir I. Titorenko

Int. J. Mol. Sci. 2014, 15(9), 16522-16543; https://doi.org/10.3390/ijms150916522 - 18 Sep 2014

Cited by 31 | Viewed by 12997

Abstract

Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile [...] Read more.

Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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1479 KiB

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Are Sensory TRP Channels Biological Alarms for Lipid Peroxidation?

by Seung-In Choi, Sungjae Yoo, Ji Yeon Lim and Sun Wook Hwang

Int. J. Mol. Sci. 2014, 15(9), 16430-16457; https://doi.org/10.3390/ijms150916430 - 17 Sep 2014

Cited by 20 | Viewed by 10100

Abstract

Oxidative stress induces numerous biological problems. Lipid oxidation and peroxidation appear to be important steps by which exposure to oxidative stress leads the body to a disease state. For its protection, the body has evolved to respond to and eliminate peroxidation products through [...] Read more.

Oxidative stress induces numerous biological problems. Lipid oxidation and peroxidation appear to be important steps by which exposure to oxidative stress leads the body to a disease state. For its protection, the body has evolved to respond to and eliminate peroxidation products through the acquisition of binding proteins, reducing and conjugating enzymes, and excretion systems. During the past decade, researchers have identified a group of ion channel molecules that are activated by oxidized lipids: transient receptor potential (TRP) channels expressed in sensory neurons. These ion channels are fundamentally detectors and signal converters for body-damaging environments such as heat and cold temperatures, mechanical attacks, and potentially toxic substances. When messages initiated by TRP activation arrive at the brain, we perceive pain, which results in our preparing defensive responses. Excessive activation of the sensory neuronal TRP channels upon prolonged stimulations sometimes deteriorates the inflammatory state of damaged tissues by promoting neuropeptide release from expresser neurons. These same paradigms may also work for pathologic changes in the internal lipid environment upon exposure to oxidative stress. Here, we provide an overview of the role of TRP channels and oxidized lipid connections during abnormally increased oxidative signaling, and consider the sensory mechanism of TRP detection as an alert system. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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739 KiB

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Abnormal Unsaturated Fatty Acid Metabolism in Cystic Fibrosis: Biochemical Mechanisms and Clinical Implications

by Adam C. Seegmiller

Int. J. Mol. Sci. 2014, 15(9), 16083-16099; https://doi.org/10.3390/ijms150916083 - 11 Sep 2014

Cited by 35 | Viewed by 7386

Abstract

Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of [...] Read more.

Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of these changes, namely increased expression and activity of fatty acid desaturases. Among other effects, this drives metabolism of linoeate to arachidonate. Increased desaturase expression appears to be linked to cystic fibrosis mutations via stimulation of the AMP-activated protein kinase in the absence of functional CFTR protein. There is evidence that these abnormalities may contribute to disease pathophysiology by increasing production of eicosanoids, such as prostaglandins and leukotrienes, of which arachidonate is a key substrate. Understanding these underlying mechanisms provides key insights that could potentially impact the diagnosis, clinical monitoring, nutrition, and therapy of patients suffering from this deadly disease. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

by Alexander N. Orekhov, Yuri V. Bobryshev, Igor A. Sobenin, Alexandra A. Melnichenko and Dimitry A. Chistiakov

Int. J. Mol. Sci. 2014, 15(7), 12807-12841; https://doi.org/10.3390/ijms150712807 - 21 Jul 2014

Cited by 88 | Viewed by 9388

Abstract

In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity [...] Read more.

In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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