Editorial
New mechanisms of vascular fibrosis: Role of lysyl oxidase
José A. Páramo
Atherothrombosis Laboratory, CIMA, University of Navarra, Pamplona, Spain
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AGE: productos de glucosilación avanzada; HIF: factor inducible por hipoxia; LOX: enzima lisil oxidasa; PGE2: prostaglandina E2; ROS: especies reactivas de oxígeno; TGF-β: factor de crecimiento transformante beta.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José A. Páramo" "autores" => array:1 [ 0 => array:2 [ "nombre" => "José A." 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Adaptación española de un Consenso Europeo de Expertos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1732 "Ancho" => 2500 "Tamanyo" => 294524 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular risk classification criteria.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">4,23</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "Atherogenic Dyslipemia Working Group of the Spanish Society of Atherosclerosis and the European Expert Group" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0214916816301772" "doi" => "10.1016/j.arteri.2016.12.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0214916816301772?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529912317000444?idApp=UINPBA00004N" "url" => "/25299123/0000002900000004/v1_201707260026/S2529912317000444/v1_201707260026/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S252991231700047X" "issn" => "25299123" "doi" => "10.1016/j.artere.2017.01.005" "estado" => "S300" "fechaPublicacion" => "2017-07-01" "aid" => "402" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Clin Investig Arterioscler. 2017;29:157-65" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Vascular lysyl oxidase over-expression alters extracellular matrix structure and induces oxidative stress" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "157" "paginaFinal" => "165" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La sobreexpresión vascular de la lisil oxidasa altera la estructura de la matriz extracelular e induce estrés oxidativo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1761 "Ancho" => 2083 "Tamanyo" => 204460 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">The production of H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> is involved in the alteration of elastin structure induced by LOX over-expression. VSMC from control mice (WT) and mice transgenic for LOX (Tg) were incubated in the presence or absence of catalase (Cat) for 10 days. Elastin staining (in green) is shown in non-permeabilised VSMC. The nuclei were stained with Hoechst 33342 (blue). Bar: 20<span class="elsevierStyleHsp" style=""></span>μm. The results are shown as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SEM (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6–10; *: <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 vs WT; #: <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 vs Tg).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Saray Varona, Ana B. García-Redondo, Jose Martínez-González, Mercedes Salaices, Ana M. Briones, Cristina Rodríguez" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Saray" "apellidos" => "Varona" ] 1 => array:2 [ "nombre" => "Ana B." "apellidos" => "García-Redondo" ] 2 => array:2 [ "nombre" => "Jose" "apellidos" => "Martínez-González" ] 3 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Salaices" ] 4 => array:2 [ "nombre" => "Ana M." "apellidos" => "Briones" ] 5 => array:2 [ "nombre" => "Cristina" "apellidos" => "Rodríguez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0214916817300499" "doi" => "10.1016/j.arteri.2017.01.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0214916817300499?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S252991231700047X?idApp=UINPBA00004N" "url" => "/25299123/0000002900000004/v1_201707260026/S252991231700047X/v1_201707260026/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "New mechanisms of vascular fibrosis: Role of lysyl oxidase" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "166" "paginaFinal" => "167" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "José A. Páramo" "autores" => array:1 [ 0 => array:2 [ "nombre" => "José A." "apellidos" => "Páramo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Atherothrombosis Laboratory, CIMA, University of Navarra, Pamplona, Spain" "identificador" => "aff0005" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1164 "Ancho" => 1439 "Tamanyo" => 77765 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Factors regulating the overexpression of LOX and the collagen assembly.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Extracellular matrix (ECM) deposit is the result of a physiological response to an insult. When this becomes chronic, changes occur in the composition, structure and accumulation of components in the ECM giving rise to fibrosis, which plays a direct role in adverse remodelling. On a cardiovascular level, fibrosis alters the structure of the myocardial tissue or of the vascular wall, conferring rigidity, loss of elasticity and, ultimately, compromising the function of the tissue or organ affected. Fibrosis occurs when the synthesis of fibrillar collagen (types I and III), a fundamental component of the ECM, predominates over degradation. In hypertensive patients, rather than an increase in the collagen content, an alteration in the assembly or cross-linking of its fibres has been described, contributing to myocardial rigidity and ultimately resulting in heart failure.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Thus, fibrosis is a determining factor in vascular senescence.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Recent studies have identified molecules which play a role in the processing of collagen. Prominent among these is the enzyme lysyl oxidase (LOX), a copper-dependent amine oxidase which participates in the covalent assembly of the collagen and elastin fibres in the ECM. Additionally, LOX controls the expression of genes involved in cell migration and differentiation, and also modulates the biological activity of growth factors.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> LOX can be regulated on three levels (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): synthesis of the precursor by fibroblasts and myofibroblasts, transformation of the precursor into the mature enzyme, and direct stimulation of enzyme activity. It has been observed that the increase of reactive oxygen species (ROS) related to oxidative stress stimulates LOX activity in fibroblast cultures.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">There is clinical and experimental evidence suggesting that the deregulation of LOX could be an important factor in the development of cardiovascular diseases.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The collagen assembly impacts the quality of LOX deregulation and affects the function of the damaged tissue or organ. One important cause of heart failure, which has a five-year mortality rate of 50%, is adverse tissue remodelling accompanied by interstitial fibrosis. There are currently no effective therapies capable of halting these processes. On a myocardial level, the degree of cross-linking determines the rigidity, thickness and resistance of the degradation, all of which have a bearing on the functional properties of the left ventricle.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In patients with hypersensitive cardiopathy and chronic heart failure, an increase in LOX expression in the fibrotic myocardium has been observed, suggesting that the overexpression of LOX may significantly compromise cardiac function.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There has also been shown to be a correlation between this enzyme and circulating biomarkers for heart failure. Finally, LOX has been related with vascular risk factors, with components of metabolic syndrome and with pulmonary arterial hypertension.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In the article by Varona et al. in this edition of Clin Invest Arterioscler,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> the role of LOX overexpression on the ECM structure and on vascular oxidative stress is analysed in a murine model. To this end, the authors used transgenic mice which overexpress LOX, conducting a quantitative analysis of the internal elastic lamina, immunohistochemical studies, determination of NADPH oxidase and H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> and cultures with smooth muscle cells. The results show that transgenic mice present with alterations in the vascular collagen assembly and in the elastin structure, as well as with increased oxidative stress, detected through an increase in H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span>. Accordingly, the vascular overexpression of LOX induced the expression of elastogenic proteins in smooth muscle cells. It was also observed <span class="elsevierStyleItalic">in vitro</span> that catalase, an anti-oxidant agent, mitigated elastin fibre organisation. Taken together, the results of this interesting experimental study evince that LOX plays a fundamental role in vascular remodelling, mediated in part by oxidative stress and by an effect on the smooth muscle cells. A subsequent preclinical approach would be interesting with a view to analysing whether the inhibition of LOX over both physiopathological processes, which have a significant impact on vascular homeostasis, could be applicable to cardiovascular diseases characterised by an increase in this enzyme. In this regard, a recent murine model study found that the inhibition of LOX with antibodies, or by means of genetic manipulation, reduced stress-induced cardiac fibrosis, prevented dilatation and improved the heart's systolic and diastolic function.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> On a clinical level, the chronic administration of torasemide was effective in mitigating LOX expression, collagen assembly and rigidity in the left ventricle in patients with heart failure.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In recent years, in addition to LOX, new candidates which help in the deregulation of collagen and fibrosis have emerged.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Salient among these are Cardiotrophin-1, Galectin-3, NADPH oxidases NOX2 and 4, neutrophil gelatinase-associated lipocalin (NGAL) and microRNAs, since their excess or deficiency may result in alterations in the fibrillar collagen. It is hoped that in the coming years it will be possible to develop agents that, by selectively modulating the action of these molecules, will have enormous anti-fibrotic potential which can be transferred to the clinical setting in the short term.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1164 "Ancho" => 1439 "Tamanyo" => 77765 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Factors regulating the overexpression of LOX and the collagen assembly.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of lysysl oxidase in myocardial fibrosis: from basic science to clinical aspects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 19 | 6 | 25 |
| 2024 September | 17 | 14 | 31 |
| 2024 August | 21 | 17 | 38 |
| 2024 July | 19 | 8 | 27 |
| 2024 June | 20 | 9 | 29 |
| 2024 May | 9 | 3 | 12 |
| 2024 April | 23 | 4 | 27 |
| 2024 March | 13 | 12 | 25 |
| 2024 February | 10 | 4 | 14 |
| 2024 January | 22 | 15 | 37 |
| 2023 December | 10 | 7 | 17 |
| 2023 November | 5 | 4 | 9 |
| 2023 October | 15 | 7 | 22 |
| 2023 September | 5 | 0 | 5 |
| 2023 August | 9 | 5 | 14 |
| 2023 July | 6 | 6 | 12 |
| 2023 June | 12 | 11 | 23 |
| 2023 May | 12 | 6 | 18 |
| 2023 April | 10 | 9 | 19 |
| 2023 March | 9 | 2 | 11 |
| 2023 February | 11 | 3 | 14 |
| 2023 January | 13 | 5 | 18 |
| 2022 December | 10 | 4 | 14 |
| 2022 November | 9 | 3 | 12 |
| 2022 October | 19 | 8 | 27 |
| 2022 September | 11 | 4 | 15 |
| 2022 August | 26 | 8 | 34 |
| 2022 July | 6 | 5 | 11 |
| 2022 June | 5 | 5 | 10 |
| 2022 May | 7 | 6 | 13 |
| 2022 April | 7 | 11 | 18 |
| 2022 March | 10 | 7 | 17 |
| 2022 February | 10 | 4 | 14 |
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