List of Abbreviations - Home - Springer978-1-4020-9701... · 2017-08-26 · List of Abbreviations 2-NBDG glucose analog AA arachidonic acid ... AMP – activated protein kinase Enzyme

List of Abbreviations

2-NBDG glucose analogAA arachidonic acidACE angiotensin converting enzymeADP adenosine diphosphateAGE advanced glycation end-productsAMP adenosine monophosphateAng-2 angiopoietin-2AP-1 activator protein-1Apo apolipoproteinARB angiotensin receptor blockersAT adipose tissueATF-6 activating transcription factor-6ATP adenosine triphosphateATP III adult treatment panel IIIBBB blood-brain barrierbFGF basic fibroblast growth factorBM bone marrowBMI body mass indexBP blood pressureBRB blood-retinal barrierBUI brain uptake indexCAD coronary artery diseaseCAM chick embryo choroallantoic membranecAMP cyclic adenosine monophosphateCARDIA coronary artery risk development in young adultsCETP cholesteryl ester transfer proteincGMP cyclic guanosine monophosphateCHD coronary heart diseaseCoA coenzyme ACOMT catechol-O-methyltransferaseCOX cyclooxygenaseCREB cAMP response element binding proteinCRP C-reactive protein

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188 List of Abbreviations

CVD cardiovascualr diseaseDNA deoxyribonucleic acidEC endothelial cellsECM extracellular matrixED endothelial dysfunctionEGCG epigallocatechin-3-gallateEGF epidermal growth factorEGIR European Group of Insulin ResistanceeNOS endothelial NOSEOCs early outgrowth coloniesEPCs endothelial progenitor cellsER endoplasmic reticulumERK extracellular signal-regulated protein kinaseETC electron transport chainFFAs free fatty acidsFGF fibroblast growth factorGLUT glucose transporterGPX glutathione peroxidaseGSH glutathioneGSSG oxidized glutathioneH2O2 hydrogen peroxideHAECs human aortic endothelial cellsHASMC human aortic vascular smooth muscle cellsHAVECs human autologous venous endothelial cellsHCAECs human coronary artery endothelial cellsHDL high density lipoproteinHETE hydroxyeicosatetraenoic acidHOXA9 homeobox A9HPA hypothalamus-pituitary-adrenal cortexHRECs human retinal endothelial cellsHSL hormone sensitive lipaseHUVEC human umbilical vein endothelial cellsIκB inhibitor κB proteinsI-CAM intercellular adhesion moleculeIFNγ interferon γ

IGF-1 insulin-like growth factorIKK inhibitor of nuclear factor κB kinaseIL interleukiniNOS inducible NOSIR insulin resistanceIRAK IL-1β-mediated IL-1β receptor-associated kinaseIRE-1 inositol-requiring enzyme-1IRS insulin receptor substrateIXN isoxanthohumolJNK c-Jun amino terminal kinase

List of Abbreviations 189

LDL low density lipoproteinLOCs late outgrowth coloniesLOX lipo-oxygenasesLPS lypopolisaccharideLT leukotrieneMAO monoaminoxidaseMAPK mitogen-activated protein kinaseMAPKK MAPK kinaseMAPKKK MAPKK kinaseMCP-1 monocyte-chemoattractantprotein-1MIP1α macrophage inflammatory molecule 1α

MMP matrix metalloproteinaseMPO myeloperoxidasemRNA messenger ribonucleic acidMS metabolic syndromeMT1-MMP membrane type 1-MMPmTOR mammalian target of rapamycinNADPH nicotinamide adenine dinucleotide phosphateNAG-1 NSAID-activated gene-1NECP national cholesterol education programNEFA non-esterified fatty acidNFκB nuclear factor kappaBnNOS neuronal NOSNO nitric oxideNOS nitric oxide synthaseNox NAD(P)H oxidasesNSAID nonsteroidal anti-inflammatory drugox-LDL oxidized-LDLPAI-1 plasminogen activator inhibitor type-1PDGF platelet-derived growth factorPEDF pigment epithelium-derived factorPERK PKR-like eukaryotic initiation factor 2a kinasePG prostaglandinsPGE2 prostaglandin E2

PGI2 prostacyclinPI3K phosphoinositide-3 kinasePKA protein kinase APKB protein kinase BPKC protein kinase CPLA2 phospholipase A2

PlGF placental growth factorPNMT phenylethanolamine-N-methyl transferasePON-1 paraoxonase-1PPARγ peroxisome proliferator-activated receptor γ

PUFA polyunsaturated fatty acids

190 List of Abbreviations

RAGE receptor of advanced glycation end-productsRNS reactive nitrogen speciesROS reactive oxygen speciesS1P platelet-derived lipid sphingosine-1-phosphateSDF-1 stromal derived factor-1sdHDL small dense HDLsdLDL small dense LDLsGC soluble guanylate ciclaseSGLT glucose co-transportersSIRT sirtuinSMC smooth muscle cellsSOD superoxide dismutaseSREBP sterol regulatory element binding proteinSRH spontaneously hypertensive ratsSTAT-1 signal transducer and activator of transcription 1T2DM type 2 diabetes mellitusTGFβ transforming growth factor β

TLR toll-like receptorTNF tumour necrosis factortPA tissue type of plasminogen activatorTPL 4-hydroxy tempolTsp thrombospondinTXA2 thromboxan A2

UCP uncoupling proteinsuPA urokinase type of plasminogen activatorUPR unfolded protein responseV-CAM vascular adhesion moleculeVEC vascular endothelial cellVEGF vascular endothelial growth factorVEGFR vascular endothelial growth factor receptorVLDL very low density lipoproteinVLDLR receptor of very low density lipoproteinsVSMC vascular smooth muscle cellsWHO World Health OrganizationXN xanthohumol

Glossary

Activator protein-1 Heterodimeric protein that functions as a transcription factorupregulating the transcription of genes containing the 12-O-tetradecanoylphorbol-13-acetate response element

Acute inflammation Short-term process characterized by the classic signs ofinflammation – swelling, redness, pain, heat, and loss of function – due to theinfiltration of the tissues by plasma and leukocytes

Adenosine Multifunctional endogenous nucleoside that modulates many biochem-ical processes, such as energy transfer – as adenosine triphosphate (ATP) andadenosine diphosphate (ADP) – as well as in signal transduction as cyclic adenosinemonophosphate, cAMP. It is also described as an inhibitory neurotransmitter

Adipocyte Primary cell type that composes the adipose tissue, specialized instoring lipids and produces specific secretions

Adipogenesis Process of differentiation of adipocyte precursor cells, orpreadipocytes, into mature adipocytes

Adipokine Cytokine secreted by the adipose tissue

Adiponectin Protein hormone secreted mainly by the adipose tissue, involded inmetabolic regulation of carbohydrate and lipid metabolism; it is decreased in obesestates

Adrenaline Also known as epinephrine; a hormone mainly secreted by adrenalmedulla, involved in metabolic and cardiovascular homeostasis

Adult vasculogenesis Postnatal adaptation of the process of embryonic vasculoge-nesis, in which circulating Endothelial Progenitor Cells are mobilized from the bonemarrow to the peripheral circulation and to neovascular sites, where they participatein the development of vascular networks by differentiating into mature endothelialcells

Advanced glycation end-products Molecules modified from the spontaneous reac-tion with carbohydrates commonly found in tissues of diabetics

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192 Glossary

Aldosterone Hormone secreted by the adrenal cortex which affects blood pressureand saline balance

Adrenoceptor Class of G protein-coupled receptors through which noradrenalineand adrenaline act as important neurotransmitters and hormones in the centralnervous system and in the periphery

Alpha 2-adrenoceptor Subtype of alpha adrenoceptor

Allostasis The ongoing adaptive efforts of the body to maintain homeostasis inresponse to stressors

AMP – activated protein kinase Enzyme expressed in a number of tissues thatplays a role in cellular energy homeostasis

Android obesity Also know as “apple-shaped obesity”; obesity of the male typethat shows a dominant visceral and upper thoracic distribution of adipose tissue

Angiogenesis Complex multistep process that enables the formation of new bloodvessels from pre-existing ones

Angiopoietin Protein that plays a role in angiogenesis and vascular development.Angiopoietins bind to specific receptors at the endothelial cell membrane mediatinginteraction between endothelium and extracellular environment

Angiotensin Family of peptides that act as potent direct vasoconstrictors to narrowblood vessels; stimulates the release of aldosterone from the adrenal cortex

Angiotensin converting enzyme inhibitors Drugs that inhibit the production ofangiotensin II and lower blood pressure

Angiotension receptor blockers Medications that block the action of angiotensinII, resulting in blood vessels dilation and reduction in blood pressure

Antioxidants Natural or synthetic substances that prevent or delay any processesof oxidation that can be damaging to cells and tissues

Apoptosis Programmed cell death; occurs when a cell is damaged beyond repair.Involves a series of biochemical events leading to a variety of cellular morphologicalchanges, characterized by cleavage of chromosomal DNA, chromatin condensation,and fragmentation of both the nucleus and the cell

Atherosclerosis Chronic inflammatory condition in which arteries undergo gradualintima thickness, causing decreasing elasticity, narrowing, and reduced blood supply

Bax Pro-apoptotic protein of the Bcl-2 gene family; key component for cellularapoptosis through mitochondrial stress. Increases membrane permeability, leading

Glossary 193

to the release of cytochrome c from mitochondria, activation of caspase-9 andinitiation of the caspase activation pathway for apoptosis

Beta 2-adrenoceptors Subtype of beta adrenoceptor

11 beta-hydroxy-steroid dehydrogenase Enzyme that catalyzes the interconver-sion of active glucocorticoids (such as cortisol and corticosterone) and their inactiveforms (such as cortisone and 11-dehydrocorticosterone)

Bioavailability Measurement of the extent of certain substance that reaches thesystemic circulation and is available at the target site

Bone marrow The soft, living tissue that fills most bone cavities and containshematopoietic stem cells, from which all red and white blood cells evolve, andmesenchymal stem cells

Catecholamines Amines derived from tyrosine that act as neurotransmitters orhormones; the most important are adrenaline, noradrenaline and dopamine

cAMP response element-binding protein Transcription factor that binds to DNAsequences called cAMP response elements to increase or decrease the transcriptionof certain genes

Catechol-o-methyltransferase Key enzyme in the degradation of catechols, suchas catecholamines, by transfering a methyl group from adenosylmethionine

CD133 Also known as AC133; 97 kDa cell surface glycoprotein with 5 transmem-brane domains, expressed by hematopoietic, neural and embryonic stem cells andhematopoietic and endothelial progenitor cells. It was also found in several tumours,including leukemias and brain tumours

CD34 Cluster of differentiation; 120kDa transmembrane glycoprotein cell sur-face present in hematopoietic stem and progenitor cells, Endothelial ProgenitorCells and mature endothelial cells. Potential adhesion molecule with a role inearly hematopoiesis by mediating the attachment of stem cells to the bone marrowextracellular matrix or directly to stromal cells

Cell senescence The limited capacity of cells to divide beyond a finite number ofpopulation doublings (finite growth potential). Irreversible growth-arrest state thatdepends on the age or cell doublings of a cell

Cell therapy Describes the process of introducing new cells into a tissue in orderto treat a specific pathology; there are several potential types of cell therapy: usingautologous (from the patient) or allogeneic (from another donor) hematopoieticstem or progenitor cells; mesenchymal stem cells; embryonic stem cells; EndothelialProgenitor Cells; differentiated functional cells; transdifferentiated cells

194 Glossary

Central obesity Accumulation of visceral adipose tissue related to increased inci-dence of metabolic disease; it is considered an important component of the metabolicsyndrome

Chelation Binding or complexation of a bi- or multidentate ligand to a substrate(often a metal ion). These ligands, which are often organic compounds, are calledchelants, chelators, chelating agents, or sequestering agent. The ligand forms achelate complex with the substrate through more than one coordination site

Chemokine Small protein or peptide molecule that activates immune cells andstimulates their migration into the site of aggression

Chronic inflammation Pathological condition characterised by concurrent activeinflammation resulting in tissue malfunction; the inflamed tissue is characterized bymononuclear cell infiltration (monocytes, macrophages, lymphocytes, and plasmacells), signs of angiogenesis and fibrosis

Chronobiology The study of how day/night related rhythms are influenced byliving pacemakers within organisms

Circadian rhythm Biological cycle that takes about 24 hours in order to becompleted

Collagen fibres Tough bundles of collagen, also called white fibres, which arethe most characteristic constituent of the connective tissue, supporting tissues andproviding cell structure from the outside

Complement system Complex series of blood protein whose action supports thework of antibodies

Cortisol Also known as hydrocortisone; the most important and most potent glu-cocorticoid in humans; produced in the outer layer of the adrenal glands

Glucocorticoids A class of steroid hormones that, in addition to playing a cen-tral role in the stress response, are involved in metabolic and anti-inflammatoryresponses

Cortisone Derived from cortisol; differently from cortisol, it does not bind to themineralocorticoid receptor

C-reactive protein Acute phase protein produced by the liver and adipose tissue,that appears in plasma and is used as marker of inflammation

Crown-like structures Common formation in the adipose tissue of obese animals;several macrophages associated in a configuration that resembles a crown arounddead adipocytes

Cyclooxygenases Enzymes that catalize the formation of prostanoids from arachi-donic acid. Cyclooxigenases are mainly involved in inflammatory response

Glossary 195

Cytokines Powefull chemical substances, proteins or glycoproteins, involved incellular communication

Dendritic cell Immune cell with highly branched extensions that engulfs foreignbodies and is involved in antigen presentation to T lymphocytes

Dyslipidaemia Disruption (generally increase) in the amount of blood lipids oftencaused by diet and life-style habits

Eicosanoids Signalling molecules produced from oxygenation of twenty-carbonessential fatty acids that participate in inflammation or immunity, and function asmessengers

Endocrine Internal or hormonal secretion; endocrine glands secrete hormonesdirectly into the circulatory system that are involved in the regulation of metabolism,growth, development and puberty, tissue function, and also play a part in determin-ing mood

Endoplasmic reticulum stress Situation caused by the accumulation of unfoldedproteins in the endoplasmic reticulum lumen that results in cell specific responsesrelated to repair, survival or death

Endothelial cells Unilayer of cells that line the inner surface of the vasculature.Endothelial cells are in contact with blood flow

Endothelial dysfunction Alterations on the normal biochemical processes car-ried out by endothelial cells, where their functions are shifted towards reducedvasodilation, a pro-inflammatory state, with prothrombic properties

Endothelial Progenitor Cells Bone marrow-derived subtype of progenitor cellswith analogous properties to embryonic angioblasts, which may be recruited to theperipheral circulation and differentiate into functional mature endothelial cells, invitro and in vivo

Estrogens A generic term for the female sex steroid hormones. In humans, estrogenis formed in the ovary, possibly the adrenal cortex, the testis and the fetoplacentalunit; responsible for initiation of estrus and for the development of secondary sexualcharacteristics in the female

Euglycaemic clamp Also known as the euglycaemic insulin clamp, the euglycemichyperinsulinaemic clamp, or the glucose clamp; provides steady-state measures ofinsulin action

Fatty acid-binding protein 4 Also called adipocyte protein-2, is a carrier for fattyacids expressed in adipocytes and macrophages

Fibroblasts Cells of connective tissue that synthesise and secrete collagen fibres,maintaining the extracellular matrix and providing a structural framework for manytissues. They occur in various shapes, such as stellate and spindle-shaped

196 Glossary

Free Radical An atom or molecule with an unpaired electron in its outermost shelland capable of independent existence. Produced in normal cellular processes, byenvironmental factors (pollutants, drugs) and as by-products of the metabolism.Chemically unstable, exhibit, however, very distinct reactivities, and typically initi-ate autocatalytic reactions which generate more free radicals

Free Radical Scavenger Free radical inactivator that reacts with free radicals inany biological system, donating electrons or H-atoms and given rise to less reactiveproducts derived from both, the radical and the scavenger

Ghrelin Appetite-stimulating hormone that is mainly secreted by cells lining thefundus of the human stomach

Gout A condition characterized by abnormally elevated levels of uric acid in theblood

GLUT Or SLC2 gene family are facilitated glucose transporters, being thus respon-sible for the downhill, passive transport of glucose across cell membranes, i.e.these transporters speed up or facilitate the equilibration of the sugar across amembrane. Prime examples include GLUT1, involved in the transport of glucoseacross the endothelial cells of the blood–brain barrier, and GLUT4, responsible forinsulin-stimulated glucose uptake into skeletal muscle. The distribution of GLUTtransporters in mammalian cells is widespread. GLUT1, GLUT3, and GLUT4 havea higher affinity for glucose, with Km values around 2 mM, whereas GLUT2 has alower affinity for glucose (Km around 20 mM)

Growth factor Family of polypeptides or biological factors that control cellulargrowth, proliferation and differentiation

Hematopoietic progenitor cells Hematopoietic cells that can differentiate intomature cells, but which lack the capacity to self-renew. Hematopoietic progeni-tor cells are derived from hematopoietic stem cells and are intermediate to theproduction of mature cells

Hematopoietic stem cells Cells that have the capacity to self-renew and to dif-ferentiate into more mature cells. Give rise to all red and white blood cells andplatelets; are defined by their ability to replace the bone marrow system followingits obliteration (for example, by g-irradiation) and can continue to produce matureblood cells

High density lipoproteins Lipoprotein of blood plasma that is composed of ahigh proportion of protein with little triglyceride and cholesterol and that is asso-ciated with decreased probability of developing atherosclerosis – called also alpha-lipoprotein.

Homeobox A9 gene Sequence-specific transcription factor, which belongs to thehomeobox (HOX) family of genes, plays an important role in hematopoiesis;

Glossary 197

gene aberrant expression has been shown to be important in the development ofleukaemia

Homeostasis The maintenance of a relatively constant internal environment in aliving organism

Hormone Chemical substance, usually a peptide or steroid, synthesized in a gland,secreted into the body fluids and carried to target cells, which respond with analteration in their metabolism

Hydrophilicity Refers to a physical property of a molecule that can transientlybond with water (H2O) through hydrogen bonding. Hydrophilic molecule is onethat is typically charge-polarized and capable of hydrogen bonding, enabling it todissolve more readily in water than in oil or other hydrophobic solvents

Hydrophobicity Refers to the physical property of a molecule that is repelled froma mass of water. Hydrophobic molecules tend to be non-polar and thus prefer otherneutral molecules and nonpolar solvents

Hyperglycaemia Presence of high levels of glucose in the blood plasma

Hyperinsulinaemia Excess levels of blood circulating insulin

Hyperleptinemia Elevated plasma levels of leptin

Hyperplasia Tissue growth through the increase in the number of cells

Hypertension Persistently high arterial blood pressure. Hypertension may have noknown cause (essential or idiopathic hypertension) or be associated with other pri-mary diseases (secondary hypertension). This condition is considered a risk factorfor the development of heart disease, peripheral vascular disease, stroke and kidneydisease

Hypertrophy Tissue growth through the increase in cell size

Hyperuricaemia Excess content of uric acid in the blood

Hypothalamus-pituitary-adrenal cortex (HPA) axis A neuroendocrine systemthat controls reactions to stress and regulates other physiological processes, suchas digestion, immune response, mood, and energy disposal

Hypoxia Deficiency in oxygen supply in a cell, tissue or organ

Hypoxia inducible factor-ααα Transcription factors that respond to decrease inavailable oxygen in the cell

Immune cells White blood cells or leukocytes that originate from the bone marrow,including antigen presenting cells, such as dendritic cells, T and B lymphocytes, and

198 Glossary

neutrophils, among many others; defend the body against infectious disease andforeign macromolecules

Immune response Reaction of the immune system to foreign substances

Inflammation A physiological response of the organism to harmful stimuli, namelyinfection or tissue injury; classical signs involve redness, swelling, heat and pain

Inhibitor of nuclear factor κκκ B kinase Kinase that phosphorylates the inhibitorof nuclear factor κ B protein and terminates the sequestration of that nucleartranscription factor, allowing its effects on gene expression

Innate immunity Immune system function that is inborn and provides an all-purpose defence against harmful stimuli

Insulin receptor Belongs to the large class of tyrosine kinase receptors and inducesa cellular response by phosphorylating proteins on their tyrosine residues. The IR isknown to phosphorylate several proteins in the cytoplasm, including insulin receptorsubstrates (IRSs)

Insulin receptor substrate Downstream molecule in the insulin signalling path-way that is phosphorylated by insulin receptor in tyrosine residues after its activationby insulin

Insulin resistance Condition in which a higher amount of insulin is needed to pro-duce the normal response to this hormone that often leads to the metabolic syndromeand type 2 diabetes

Insulin resistance Insulin resistance is the condition in which normal amounts ofinsulin are inadequate to produce a normal insulin response from fat, muscle andliver cells

Interleukin Major group of cytokines initially reported to be secreted by leuco-cytes with communication functions

Ischemia Relative or absolute restriction of blood supply to an organ with resultantdamage or dysfunction of the tissue

Isoprenaline A synthetic beta-sympathomimetic derived from adrenaline

Jun N-terminal kinase Kinase that binds and phosphorylate c-Jun on serine resi-dues in response to stress stimuli, such as cytokines, ultraviolet irradiation, heatshock, and osmotic shock; belong to mitogen-activated protein kinase family

Leptin 16 kDa adipose-derived protein hormone that plays a key role in regulat-ing energy intake and energy expenditure, including appetite and metabolism; it isaugmented in obese states

Glossary 199

Leucocytes Cells of the immune system defending the body against both infectiousdisease and foreign materials

Lipid droplet Also called adiposome, is the lipid storage organelle in cell, espe-cially large in adipocytes

Lipodystrophy Medical condition characterized by lack and/or altered body dis-tribution of adipose tissue

Lipogenesis Encompasses the process of fatty acid synthesis from glucose andtriglyceride synthesis, to store in lipid droplets within the cell or incorporate inVLDL particles to secrete to the blood stream

Lipolysis Breakdown of triglycerides with resulting release of free fatty acids andglycerol

Lipophilicity Refers to the ability of a chemical compound to dissolve in fats, oils,lipids, and non-polar solvents. These substances tend to dissolve in other lipophilicsubstances

Lipotoxicity Adverse effects resulting from the accumulation of lipids in non-adipose cells

Lipoxins Anti-inflammatory mediators derived from arachidonic acid

Low-density lipoprotein Type of lipoprotein that transports cholesterol and triglyc-erides from the liver to peripheral tissues. High levels of LDL are associated withan increased risk of atherosclerosis and cardiovascular disease

Lymphocyte Small white blood cell produced in lymphoid organs and essential toimmune defences

Macrophage Large and versatile immune cell that phagocytises invading pathogensand other foreign bodies working both on non-specific defence or collaborating incell-mediated immunity; are originated from blood monocytes

Mast cells Granulocyte resident in several types of tissues, whose contents in hep-arin and histamine contribute to the symptoms of allergy, but are also involved inwound healing

Matrix metalloproteinase Zinc-dependent endopeptidase able to degrade extra-cellular matrix components

Metanephrine O-methylated metabolite of adrenaline

Microalbuminuria Leakage of small albumin amounts into the urine

Mineralocorticoid receptors Hormone- activated transcriptional factors that reg-ulate a wide variety of physiological processes ranging from organ development

200 Glossary

and differentiation to mood control and stress response; bind both aldosterone andcortisol with equal affinity

Mitochondrial dysfunction Within eukaryotic cells mitochondria provide mostof the ATP by oxidative phosphorylation. Consequently, mitochondrial dysfunc-tion contributes to a wide range of human pathologies, including neurodegenerativediseases, ischaemia-reperfusion injury in stroke and heart attack, diabetes and thecumulative degeneration associated with ageing. This mitochondrial dysfunctioncauses cell damage and death by compromising ATP production, disrupting calciumhomeostasis and increasing free radical fluxes and oxidative stress

Mitogen-activated protein kinases Serine/threonine-specific protein kinases thatrespond to extracellular stimuli (mitogens) and regulate various cellular activities,such as gene expression, mitosis, differentiation, and cell survival/apoptosis

Monoaminoxidase Enzyme that catalyzes the degradation of naturally occurringmonoamines, such as catecholamines, by oxidative deamination

Monocyte chemoattractant protein-1 Small cytokine belonging to the CCchemokine family that recruits monocytes, memory T lymphocytes and dendriticcells to sites of tissue injury and infection

Mononuclear cells Non-specific term referring to lymphocytes and plasma cellsand macrophages; literally means cells without lobed nuclei (i.e. not neutrophils,eosinophils or basophils)

NAD(P)H oxidases Enzymes that catalyze oxidoreductase reactions, using oxygenas the electron acceptor molecule

Neovascularisation Formation of blood vessels de novo

Neuroendocrine Interaction between the nervous and endocrine system, whichsecretes neurotransmitter, neuromodulator or neuropeptide hormones into the periph-eral circulation in response to a neural stimulus

Neutrophil White blood cell that is an abundant and important phagocyte

Nitric oxide synthase Family of enzymes that synthesize nitric oxide (NO) fromL-arginine, NADPH and O2. NOS play a crucial role in the nervous, immune andvascular systems

Non-esterified fatty acids Fatty acids released after lipolysis to the blood streamwhere they can be found bound to albumin

Non-phlogistic Non-inflammatory (phlogistic, from the greek phogizo means flame,set fire, inflammation)

Noradrenaline Also known as norepinephrine; the major neurotransmitter of thesympathetic nervous system; mainly involved in cardiovascular homeostasis

Glossary 201

Nuclear factor κκκ B Transcription factor found in almost all animal cell typesinvolved in cellular responses to stimuli such as stress, cytokines, free radicals,ultraviolet irradiation and bacterial or viral antigens; plays a key role in regulatingthe immune response to infection

Oxidative stress Imbalance in the dynamic equilibrium between oxidants andantioxidants in biological systems that favours the formers, potentially leadingto damage. Recent updates of the concept emphasize the occurrence of compar-timentalized cellular redox circuits and individual signalling, rather than globalbalances

Oxidized low-density lipoproteins Fraction of the LDL population that has suf-fered oxidative modification of its lipid and apoB protein content, increasing itsatherogenic potential. The oxidation of LDL particles leads to its internalizationby macrophages in the intima space of arterial wall via scavenger receptors. Uponaccumulation the macrophage-loaded LDL constitute the precursors of fatty streaks.High levels of oxidized LDL appear to be also associated with three of the individualcomponents of metabolic syndrome, such as obesity, hypertriglyceridemia, and highfasting glucose

p38 MAPK Class of mitogen-activated protein kinases which are responsive tostress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmoticshock and are involved in cell differentiation and apoptosis

Pericytes Relatively undifferentiated mesenchymal-derived cell that supports ves-sels (capillaries). Pericytes can differentiate into smooth muscle cells, fibroblasts ormacrophages, and play a relevant role in vessel stabilization and angiogenesis

Peroxisome proliferator-activated receptor γγγ Nuclear receptor protein activatedby prostaglandin J2 and thiazolidinediones that functions as a transcription factorregulating the expression of genes upon heterodimerization with the retinoid Xreceptor and further binding to proliferator hormone response elements to regulategenes involved in adipocyte differentiation and inflammation

Peroxynitrite anion Oxidant and nitrating agent that can damage a wide array ofmolecules in cells, including DNA and proteins

Phagocytosis Process by which one cell engulfs another cell or a large particle

Phenylethanolamine- N- methyl transferase Enzyme found in the adrenal medullathat converts noradrenaline into adrenaline

PI3 Kinase pathway Catalyzes the production of phosphatidylinositol-3,4,5-trisphosphate, in cell survival pathways, regulation of gene expression and cellmetabolism, and cytoskeletal rearrangements

202 Glossary

Plasminogen activator inhibitor type-1 Major inhibitor of tissue (tPA) andurokinase-type (uPA) plasminogen activators, which play a relevant role in fibri-nolysis. Plasminogen activator inhibitor-1 is a serine protease inhibitor (Serpin)

Polyphenols Large family of natural compounds widely distributed in plant foods;are the most abundant antioxidants in the diet

Preadipocyte Adipocyte precursor cells that resemble fibroblasts but are commitedto the adipocyte lineage

Prooxidant Chemicals or substances that induce oxidative stress, either throughcreating reactive oxygen species or by inhibiting antioxidant systems

Protectins Family of docosahexaenoic acid-derived mediators possessing a conju-gated triene structure as a distinguishing feature; involved in inflammation resolu-tion

RAGE Member of the Immunoglobulin superfamily which binds a variety ofligands including advanced glycation end products (AGEs) and amyloid fibrils;expressed by endothelium, mononuclear phagocytes, smooth muscle and neurons.It may be involved in a range of pathological conditions including diabetes andAlzheimer’s disease

Reactive oxygen species Reactive molecules derived from molecular oxygen (ROS).ROS include either free radicals (such as superoxide and hydroxyl radicals) andnon-radicals (such as hydrogen peroxide). ROS play a role in cell signalling and itssteady-state concentration increase during oxidative stress

Reactive nitrogen species Reactive molecules derived from nitric oxide (RNS).Formed upon reaction of nitric oxide with superoxide radical (peroxynitrite anion)or oxygen (e.g. nitrite radical). Are responsible for the indirect noxious effects ofnitric oxide

Redox Signalling Free radical and oxidant-dependent post-translational modifica-tion of regulatory proteins that use redox chemistry and transduce an oxidant signalinto a biological response

Renin Enzyme produced by the kidneys that regulates the volume of fluids inthe body and blood pressure; catalyzes the convertion of angiotensinogen intoangiotensin II

Renin-angiotensin system System of hormones and enzymes that plays an impor-tant role in regulating blood pressure and the body’s balance of fluids and elec-trolytes

Resolution Complete restoration of the inflamed tissue to its normal status includ-ing carried out by anti-inflammatory mediators, neutrophil apoptosis and phagocy-tosis by macrophages with posterior clearance through lymphatics

Glossary 203

Resolvins Lipid derived resolution-phase interaction products carrying bioactivity

SGLT Sodium-coupled glucose cotransporters responsible for active glucoseuptake. SGLT transporters belong to the SLCA5 gene family. The most well-knownmember is SGLT1, which is responsible for the active transport of glucose acrossthe brush border membrane of the small intestine. SGLT1 is a high-affinity, Na+-dependent and phloridzin-sensitive glucose co-transporter, and actively transportsglucose and galactose with similar and high affinities (around 0.1-0.6 mM)

Sirtuin 1 gene Encodes for an enzyme which deacetylates proteins that contributeto cellular regulation (reaction to stressors, longevity)

Smooth muscle cells Type of nonstriated muscle cells present in the tunica medialayer of arteries and veins

Somatostatin Also known as somatotropin release-inhibiting factor; a neuropep-tide, widely distributed throughout the central nervous system and periphery, thatacts primarily as a negative regulator of neurotransmission, cell secretion and cellproliferation

Statin Class of drugs commonly used to lower cholesterol levels by inhibiting theenzyme HMG-CoA reductase, which is the rate-limiting enzyme of the mevalonatepathway of cholesterol synthesis

Sterol regulatory element-binding protein Transcription factor involved in theactivation of genes involved in lipogenesis and very low density lipoprotein excre-tion

Stromal Derived Factor -1 Small cytokine belonging to the chemokine family C-X-C motif ligand 12 (CXCL12), which binds to receptor CXCR4. Strongly chemo-tactic for lymphocytes; during embryogenesis directs the migration of hematopoi-etic cells from foetal liver to the bone marrow and the formation of large bloodvessels; in adulthood plays an important role in angiogenesis by inducing therecruitment of Endothelial Progenitor Cells

Substance P Short-chain polypeptide that functions as a neurotransmitter espe-cially in the pain fiber system; also involved in immune/hematopoietic systemmodulation

Superoxide anion Also called superoxide radical. The one-electron reduction prod-uct of molecular oxygen. Limited reactivity as compared with other more oxidizingradicals, such as hydroxyl, peroxyl and alkoxyl radicals. Usually, produced as aby-product of certain metabolic reactions but also on purpose by biological defensemechanisms

Sympatho-adrenomedullary axis Sympathetic branch of the autonomic nervoussystem; involved in body homeostasis, blood pressure, heart rate, energy balanceand intermediary metabolism

204 Glossary

Systemic low-grade chronic inflammation State of prolonged mild chronicinflammatory response characterised by a 2- to 3-fold increase in plasma concentra-tions of cytokines and acute phase proteins

Telomerase Enzyme composed of a catalytic protein component and an RNA tem-plate and that synthesizes DNA at the ends of chromosomes and confers replicativeimmortality to cells

Telomere Specialized nucleic acid structure found at the end of a chromosome.Associated with a characteristic DNA sequence that is replicated in a special way.A telomere counteracts the tendency of the chromosome to shorten with each roundof replication

Thiazolidinediones Also called glitazones, are drugs used in the therapy of type2 diabetes that act by binding to peroxisome proliferator-activated receptor γ andactivating the transcription of specific genes involved in lipid and carbohydratemetabolism, adipocyte differentiation, angiogenesis and inflammation

Toll-like receptors Receptors that recognize microbial patterns and represent agermline encoded non-self recognition system that is involved in first line defenceagainst pathogens

Transforming growth factor βββ Peptide with a role in the control of proliferation,cellular differentiation and other functions in most cells

Tumour necrosis factor ααα Cytokine that stimulates the acute phase reaction reg-ulating apoptotic cell death, cellular proliferation, differentiation, inflammation,tumorigenesis, and viral replication

Type 2 diabetes mellitus Also known as non-insulin-dependent diabetes mellitusor adult-onset diabetes; is a metabolic disorder primarily characterized by insulinresistance, relative insulin deficiency, and hyperglycaemia. These alterations leadto damage and functional impairment of many organs, most importantly in thecardiovascular system

Unfolded protein response Cellular stress response related to the endoplasmicreticulum activated in response to an accumulation of unfolded or misfolded pro-teins in the lumen of endoplasmic reticulum; constitutes a graded series of actionsrelated to restoration of the normal function of the cell by halting protein translationand increasing the production of chaperones, and if not enough, initiates apoptosis

Urokinase type of plasminogen activator Serine protease enzyme that triggers aproteolysis cascade by activating plasminogen into plasmin, participating hence inthrombolysis or extracellular matrix degradation

Vascular Endothelial Growth Factor Family of growth factors, VEGF or VEGF-A is the key regulator molecule of the processes of vasculogenesis and angiogenesis,during embryogenesis and adulthood. By interaction with its receptors tyrosine

Glossary 205

kinase, it mediates endothelial cell survival, proliferation, migration and differ-entiation during angiogenesis. Induces the mobilization and recruitment of bonemarrow-derived Endothelial Progenitor Cells in vasculogenesis

Vascular repair Endogenous capacity to restore the functional integrity of a dam-aged endothelial monolayer, by the activation of the processes of angiogenesis andadult vasculogenesis

Vasculogenesis De novo vessel formation occurring during embryonic develop-ment in which angioblasts differentiate in endothelial cells that assemble into theprimary capillary plexus of the embryo

Very low density lipoproteins Type of lipoprotein involved in the transport ofendogenous lipids (triglycerides, phospholipids, cholesterol and cholesteryl esters),from the liver into extrahepatic tissues

Index

AActivator protein-1, 68, 159Acute inflammation, 156Adenosine, 5, 9, 129, 137Adipocyte, 1, 3–5, 7, 12, 34–37, 54, 69–73, 75,

77, 78, 90, 93, 106, 107, 133, 134, 166, 167Adipogenesis, 7Adipokine, 3, 34, 54, 66, 70, 93, 106–108, 124Adiponectin, 3, 5, 34, 70, 73, 87, 88,

106–108, 167Adrenaline, 8, 9Adrenoceptor, 9Adult, vasculogenesis 102, 108, 114Advanced glycation end-products, 37, 40, 69,

91, 108, 164Aldosterone, 5, 10Allostasis, 4, 6Alpha 2-adrenoceptor, 9AMP – activated protein kinase, 7Android obesity, 2Angiogenesis, 25, 44, 85–94, 102, 103, 105,

157, 160, 163–168, 170Angiopoietin, 87, 89, 90, 93Angiotensin, 5, 7, 25, 43–46, 48, 113Angiotensin converting enzyme inhibitors, 113Angiotensin receptor blockers, 46, 113Antioxidants, 21–24, 27–29, 34–36, 40–42,

46–48, 50, 52–55, 77, 112, 114Apoptosis, 5, 28, 37, 41, 51, 52, 67, 77, 109,

110, 112, 125, 164, 165Atherosclerosis, 25, 28, 34–36, 42, 44, 49, 52,

55, 69, 76, 85, 88, 102, 108–110, 112–114,124, 125, 140, 160, 166, 168–170, 182

BBax, 110Beta 2-adrenoceptors, 911 beta-hydroxy-steroid dehydrogenase, 7

Bioavailability, 44, 111, 112, 148,154–156, 170

Bone marrow, 90, 103, 162

CcAMP response element-binding protein,

68, 75Catecholamines, 6–9, 70Catechol-o-methyltransferase, 8, 9, 153, 155CD133, 104, 105CD34, 102–105, 111Cell senescence, 109Cell therapy, 94, 105Central obesity, 3, 7, 36, 66Chelation, 148, 153Chemokine, 67, 69, 70, 72, 73, 103, 157, 160Chronic inflammation, 65–78, 87, 168Chronobiology, 4–6, 10, 12Circadian rhythm, 10Collagen fibres, 106Complement system, 70Cortisol, 5–9Cortisone, 7C-reactive protein (CRP), 3, 10, 36, 73, 169Crown-like structures, 72Cyclooxygenases, 23, 88, 157Cytokines, 25, 37, 68, 72, 73, 78, 87, 162, 163

DDendritic cell, 69Dyslipidaemia, 34, 48–52, 55, 85, 87, 106,

108, 110, 112, 182

EEicosanoids, 43, 67, 70, 157Endocrine, 9, 12, 70, 77, 106, 107, 124Endoplasmic reticulum stress, 35, 66, 77Endothelial cells, 29, 43, 51, 52, 68, 70, 86,

89, 102, 104, 110, 124–126, 129, 130, 135,137, 138, 159, 169

207

208 Index

Endothelial dysfunction, 44–46, 48, 102, 105,124, 160

Endothelial progenitor cells, 90, 101–114Estrogens, 8Euglycaemic clamp, 3

FFatty acid-binding protein 4, 71Fibroblasts, 90, 106, 164Free radical, 21–28, 38, 42–44, 55, 125, 134,

135, 148, 153, 169Free radical scavenger, 46

GGhrelin, 88, 89Glucocorticoids, 7GLUT, 127, 128, 130, 133, 135Gout, 2Growth factor, 5, 25, 37, 43, 51, 67, 87–90, 92,

94, 103, 106, 125, 130, 135–137, 139, 159,160, 162–164

HHematopoietic progenitor cells, 103Hematopoietic stem cells, 104High density lipoproteins (HDL), 11, 47, 48,

49, 51–54, 66, 110, 168, 184Homeobox A9 gene, 111Homeostasis, 8, 29, 41, 65, 66, 76, 78, 86, 88,

93, 103, 105, 111, 124, 126, 139, 182Hormone, 6, 9, 35, 43, 70, 75, 86, 88, 89, 93,

106–108, 166Hydrophilicity, 154Hydrophobicity, 153Hyperglycaemia, 2, 35–41, 47, 48, 51, 55,

69, 75, 86, 92, 108, 109, 112, 123–125,131–135, 137–139, 167, 184

Hyperinsulinaemia, 36, 87, 124Hyperleptinemia, 107Hyperplasia, 73Hypertension, 1, 2, 4, 7, 10, 33–35, 41–48,

55, 66, 87, 88, 101, 106, 108, 111, 112,123–125, 137–140, 182–185

Hypertrophy, 1, 5, 42, 45, 65, 66, 73, 76, 185Hyperuricaemia, 87Hypothalamus-pituitary-adrenal cortex (HPA)

axis, 6Hypoxia, 5, 9, 37, 76, 77, 85, 87–89, 93, 123,

124, 126, 127, 129, 137, 138, 163, 164Hypoxia inducible factor-α, 87, 164

IImmune cells, 71, 88, 106, 157Immune response, 68–71, 163

Inflammation, 4, 22, 25, 65–78, 85–89, 91, 93,109, 124, 136, 137, 147, 148, 156, 157,159, 160, 162, 165–170

Inhibitor of nuclear factor κ B kinase, 68, 157Innate immunity, 68–70, 72Insulin receptor, 74, 75Insulin receptor substrate, 74Insulin resistance, 1–3, 12, 33–35, 38–41,

48–50, 54, 55, 65, 66, 74–78, 87, 90, 93,101, 105, 106, 108, 109, 124, 131, 166, 167

Interleukin, 3, 10, 67, 136, 157Ischemia, 23, 92, 103, 160, 165Isoprenaline, 9

JJun N-terminal kinase (JNK), 4, 68, 75–78,

162, 164

LLeptin, 5, 34, 35, 54, 70, 87–89, 93, 101, 106,

107, 167Leucocytes, 67Lipid droplet, 72Lipodystrophy, 71Lipogenesis, 75Lipolysis, 3, 6, 50Lipophilicity, 153Lipotoxicity, 74Lipoxins, 67Low-density lipoprotein (LDL), 35, 48–55, 74,

104, 110, 111, 113, 167–169, 185Lymphocyte, 67, 69, 72, 157, 163

MMacrophage, 4, 35, 49, 50, 66–68, 71–73, 77,

104, 156–163, 166–169Mast cells, 67, 69Matrix metalloproteinase, 25, 71, 88, 89, 103,

104, 109, 160, 163, 165, 168Metanephrine, 8, 9Microalbuminuria, 42, 87Mineralocorticoid receptors, 7Mitochondrial dysfunction, 38, 39, 41Mitogen-activated protein kinases, 25, 29, 68,

70, 74, 75, 78, 109, 157, 158, 162–165Monoaminoxidase, 8Monocyte chemoattractant protein-1, 35, 70Mononuclear cells, 46, 47, 104, 162, 168

NNAD(P)H oxidases, 23, 25, 38, 43–46, 88Neovascularisation, 86, 94, 101, 103–105,

165, 168Neuroendocrine, 107Neutrophil, 67, 156, 161

Index 209

Nitric oxide synthase, 23, 26, 42–44, 87–89,137, 157–159

Non-esterified fatty acids, 66Non-phlogistic, 67Noradrenaline, 8Nuclear factor κB (NFκB)), 10, 25, 29,

40, 68–70, 76–78, 89, 157–162, 164,165, 167

OOxidative stress, 21–29, 33–55, 69, 75–77,

86–89, 106, 108–112, 125, 134, 135, 147,148, 155, 159, 170

Oxidized low-density lipoproteins, 49–52,110, 169

Pp38 MAPK, 40, 68, 75, 78, 109, 158, 163, 164Pericytes, 86, 89, 129, 130, 133Peroxisome proliferator-activated receptor γ ,

71, 112, 138Peroxynitrite anion, 111, 159Phagocytosis, 72Phenylethanolamine- N- methyl transferase, 8PI3 Kinase pathway, 74, 110, 113, 160,

164, 165Plasminogen activator inhibitor type-1, 3, 35,

70, 87, 90, 91Polyphenols, 8, 28, 29, 114, 147–171Preadipocyte, 5, 7, 10, 69, 71Prooxidant, 135Protectins, 67

RRAGE 70, 109Reactive nitrogen species (RNS), 27, 28, 36,

38, 41, 125Reactive oxygen species (ROS), 22, 23,

25, 27, 28, 35, 36, 38–43, 45–47, 55,77, 88, 109–112, 125, 131, 134, 135,137, 155

Redox signalling, 24Renin, 10, 45Renin-angiotensin system, 5, 43, 44

Resolution, 67, 72Resolvins, 67

SSGLT, 126, 130, 133Sirtuin 1 gene, 29, 109Smooth muscle cells, 43, 45, 86, 124, 126, 127,

139, 164Somatostatin, 8Statin, 53, 113Sterol regulatory element-binding protein, 75Stromal derived factor-1, 103Substance P, 5, 9, 10Superoxide anion, 35, 38, 46, 47, 110, 131Sympatho-adrenomedullary axis, 6, 7Systemic low-grade chronic inflammation, 67

TTelomerase, 110, 111Telomere, 109, 112Thiazolidinediones, 74, 112Toll-like receptors, 68, 69Transforming growth factor β, 43, 67, 72, 88,

90, 162Tumour necrosis factor α (TNFα), 3, 25, 34,

35, 51, 54, 68–70, 76, 77, 94, 136, 123–7,157, 160–163, 166, 167

Type 2 diabetes mellitus, 85, 86, 91, 93, 106,108, 109, 112, 124, 166–168, 170

UUnfolded protein response, 35, 77Urokinase type of plasminogen activator,

89, 165

VVascular endothelial growth factor (VEGF), 5,

25, 87–94, 103–105, 110, 111, 113, 114,123, 125, 129, 130, 135, 136, 159, 160,163–165, 168

Vascular repair, 102, 107, 108Vasculogenesis, 101–103, 105–114Very low density lipoproteins (VLDL), 48–51,

74, 75, 90