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            0 => "COPD"
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            2 => "Damage"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">The respiratory muscles of patients with chronic obstructive pulmonary disease &#40;COPD&#41; display evidence of structural damage in parallel with signs of adaptation&#46; We hypothesized that this can only be explained by the simultaneous activation of satellite cells&#46; The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p class="elsevierStyleSimplePara elsevierViewall">The study included 8 patients with severe COPD &#40;mean &#91;SD&#93; forced expiratory volume in 1 second&#44; 33&#37; &#91;9&#37;&#93; of predicted&#41; and 7 control subjects in whom biopsies were performed of the external intercostal muscle&#46; The samples were analyzed by light microscopy to assess muscle fiber phenotype&#44; electron microscopy to identify satellite cells&#44; and real-time polymerase chain reaction to analyze the expression of the following markers&#58; insulin-like growth factor 1&#44; mechano growth factor&#44; and embryonic and perinatal myosin heavy chains &#40;MHC&#41; as markers of microstructural damage&#59; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells&#44; respectively&#59; and MHC-I&#44; IIa&#44; and IIx as determinants of muscle fiber phenotype&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">The patients had larger fibers than healthy subjects &#40;54 &#91;6&#93; vs 42 &#91;4&#93; &#956;m<span class="elsevierStyleSup">2</span>&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;01&#41; with a similar or slightly increased proportion of satellite cells&#44; as measured by ultrastructural analysis &#40;4&#46;3&#37; &#91;1&#37;&#93; vs 3&#46;7&#37; &#91;3&#46;5&#37;&#93;&#59; <span class="elsevierStyleItalic">P</span> &#62; &#46;05&#41; or expression of Pax-7 &#40;5&#46;5 &#91;4&#46;1&#93; vs 1&#46;6 &#91;0&#46;8&#93; arbitrary units &#91;AU&#93;&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;05&#41;&#46; In addition&#44; there was greater activation of satellite cells in the patients&#44; as indicated by increased expression of m-cadherin &#40;3&#46;8 &#91;2&#46;1&#93; vs 1&#46;0 &#91;1&#46;2&#93; AU&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;05&#41;&#46; This was associated with increased expression of markers of microstructural damage&#58; insulin-like growth factor 1&#44; 0&#46;35 &#40;0&#46;34&#41; vs 0&#46;09 &#40;0&#46;08&#41; AU &#40;<span class="elsevierStyleItalic">P</span> &#60; &#46;05&#41;&#59; mechano growth factor&#44; 0&#46;45 &#40;0&#46;55&#41; vs 0&#46;13 &#40;0&#46;17&#41; AU &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;05&#41;&#46; CONCLUSIONS&#58; The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation&#46; This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">Los m&#250;sculos respiratorios de los pacientes con enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41; presentan lesiones estructurales&#44; que coexisten con signos de adaptaci&#243;n&#46; Nuestra hip&#243;tesis es que esto s&#243;lo puede explicarse si se produce simult&#225;neamente la activaci&#243;n de sus c&#233;lulas sat&#233;lite&#46; El prop&#243;sito del presente trabajo ha sido valorar el n&#250;mero y la eventual activaci&#243;n de dichas c&#233;lulas&#44; as&#237; como la expresi&#243;n de marcadores de microlesi&#243;n estructural&#44; ligados a la regeneraci&#243;n&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; en el estudio a 8 pacientes con EPOC grave -media &#177; desviaci&#243;n est&#225;ndar del volumen espiratorio forzado en el primer segundo&#58; un 33 &#177; 9&#37; del valor de referencia-y a 7 controles&#44; a quienes se realiz&#243; una biopsia del m&#250;sculo intercostal externo&#46; La muestra se analiz&#243; mediante microscopia &#243;ptica &#40;fenotipo fibrilar&#41;&#44; electr&#243;nica &#40;c&#233;lulas sat&#233;lite&#41; y t&#233;cnica de reacci&#243;n en cadena de la polimerasa <span class="elsevierStyleItalic">en tiempo real</span> &#40;marcadores de microlesi&#243;n&#58; factor de crecimiento similar a la insulina de tipo 1&#44; factor de crecimiento mec&#225;nico e isoformas de cadenas pesadas de miosina &#91;MyHC&#93; embrionaria e isoformas de perinatal&#59; de presencia y activaci&#243;n de c&#233;lulas sat&#233;lite&#58; Pax-7 y m-caderina&#44; respectivamente&#59; y condicionantes del fenotipo fibrilar&#58; MyHC-I&#44; IIa y IIx&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Los pacientes tuvieron unas fibras mayores que los sujetos sanos &#40;54 &#177; 6 frente a 42 &#177; 4 &#124;a&#44; m<span class="elsevierStyleSup">2</span>&#59; p &#60; 0&#44;01&#41;&#44; con una poblaci&#243;n de c&#233;lulas sat&#233;lite conservada o ligeramente incrementada &#40;cuantificaci&#243;n ultraestructural&#58; 4&#44;3 &#177; 1&#37; frente al 3&#44;7 &#177; 3&#44;5&#37;&#44; p no significativa&#59; Pax-7&#58; 5&#44;5 &#177; 4&#44;1 frente a 1&#44;6 &#177; 0&#44;8&#44; unidades arbitrarias &#91;ua&#93;&#44; respectivamente&#44; p &#60; 0&#44;05&#41; y una mayor activaci&#243;n &#40;m-caderina&#58; 3&#44;8 &#177; 2&#44;1 frente a 1&#44;0 &#177; 1&#44;2 ua&#59; p &#61; 0&#44;05&#41;&#46; Esto se asociaba a valores aumentados de marcadores de microlesi&#243;n &#40;factor de crecimiento similar a la insulina de tipo 1&#58; 0&#44;35 &#177; 0&#44;34 frente a 0&#44;09 &#177; 0&#44;08 ua&#44; p &#60; 0&#44;05&#59; factor de crecimiento mec&#225;nico&#58; 0&#44;45 &#177; 0&#44;55 frente a 0&#44;13 &#177; 0&#44;17 ua&#44; p &#61; 0&#44;05&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">Los m&#250;sculos intercostales de pacientes con EPOC grave muestran signos indirectos de microlesi&#243;n&#44; acompa&#241;ados de la activaci&#243;n de sus c&#233;lulas sat&#233;lite&#46; Esto apunta a la presencia de ciclos continuados de lesi&#243;n y reparaci&#243;n&#44; lo que podr&#237;a explicar parcialmente la conservaci&#243;n de sus propiedades estructurales&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">This study was supported by funds from the European Union &#40;Fifth Framework Programme&#44; reference QLRT-2000-00417&#41;&#44; the Spanish Ministry of Science and Technology &#40;National R&#43;D Plan&#44; reference SAF 2001-0426&#41;&#44; the Spanish Ministry of Health &#40;Red RESPIRA&#44; reference RTIC C03&#47;11&#44; Health Research Fund&#44; Carlos III Health Institute&#41;&#44; the Spanish Society of Pulmonology and Thoracic Surgery &#40;SEPAR&#41;&#44; and the Generalitat de Catalu&#241;a &#40;2005SGR01060&#41;&#46;</p> <p class="elsevierStyleNotepara">J&#46; Mart&#237;nez-Llorens was supported by institutional funding from SEPAR&#44; the Catalan Society of Pulmonology &#40;SOCAP&#41;&#44; and the Municipal Institute for Medical Research &#40;IMIM&#44; grants for residents&#44; 2002 and 2003&#41;&#46;</p>"
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Vol. 44. Issue 5.
Pages 239-244 (January 2008)
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Vol. 44. Issue 5.
Pages 239-244 (January 2008)
Original Articles
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Activation of Satellite Cells in the Intercostal Muscles of Patients With Chronic Obstructive Pulmonary Disease
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Juana Martínez-Llorensa,b, Carme Casadevallb, Josep Lloretaa,c,d, Mauricio Orozco-Levia,b,d, Esther Barreiroa,b,d, Joan Broquetasa,b,e, Joaquim Geaa,b,d,
Corresponding author
jgea@imim.es

Correspondence: Dr J. Gea Servei de Pneumologia, Hospital del Mar-IMIM Pg. Marítim, 25-27 08003 Barcelona, Spain
a Servei de Pneumologia, Hospital del Mar-IMIM, Barcelona, Spain
b Unitat de Recerca en Múscul i Aparell Respiratori (URMAR), Hospital del Mar-IMIM, Barcelona, Spain
c Departament de Patologia, Hospital del Mar-IMIM, Barcelona, Spain
d Universitat Pompeu Fabra, CIBER de Enfermedades Respiratorias (CibeRes), Barcelona, Spain
e Universitat Autònoma de Barcelona, CIBER de Enfermedades Respiratorias (CibeRes), Barcelona, Spain
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Objective

The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) display evidence of structural damage in parallel with signs of adaptation. We hypothesized that this can only be explained by the simultaneous activation of satellite cells. The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration.

Patients and methods

The study included 8 patients with severe COPD (mean [SD] forced expiratory volume in 1 second, 33% [9%] of predicted) and 7 control subjects in whom biopsies were performed of the external intercostal muscle. The samples were analyzed by light microscopy to assess muscle fiber phenotype, electron microscopy to identify satellite cells, and real-time polymerase chain reaction to analyze the expression of the following markers: insulin-like growth factor 1, mechano growth factor, and embryonic and perinatal myosin heavy chains (MHC) as markers of microstructural damage; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells, respectively; and MHC-I, IIa, and IIx as determinants of muscle fiber phenotype.

Results

The patients had larger fibers than healthy subjects (54 [6] vs 42 [4] μm2; P < .01) with a similar or slightly increased proportion of satellite cells, as measured by ultrastructural analysis (4.3% [1%] vs 3.7% [3.5%]; P > .05) or expression of Pax-7 (5.5 [4.1] vs 1.6 [0.8] arbitrary units [AU]; P < .05). In addition, there was greater activation of satellite cells in the patients, as indicated by increased expression of m-cadherin (3.8 [2.1] vs 1.0 [1.2] AU; P=.05). This was associated with increased expression of markers of microstructural damage: insulin-like growth factor 1, 0.35 (0.34) vs 0.09 (0.08) AU (P < .05); mechano growth factor, 0.45 (0.55) vs 0.13 (0.17) AU (P=.05). CONCLUSIONS: The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation. This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle.

Key words:
COPD
Muscle dysfunction
Damage
Repair
Satellite cells
Objetivo

Los músculos respiratorios de los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) presentan lesiones estructurales, que coexisten con signos de adaptación. Nuestra hipótesis es que esto sólo puede explicarse si se produce simultáneamente la activación de sus células satélite. El propósito del presente trabajo ha sido valorar el número y la eventual activación de dichas células, así como la expresión de marcadores de microlesión estructural, ligados a la regeneración.

Pacientes y métodos

Se incluyó en el estudio a 8 pacientes con EPOC grave -media ± desviación estándar del volumen espiratorio forzado en el primer segundo: un 33 ± 9% del valor de referencia-y a 7 controles, a quienes se realizó una biopsia del músculo intercostal externo. La muestra se analizó mediante microscopia óptica (fenotipo fibrilar), electrónica (células satélite) y técnica de reacción en cadena de la polimerasa en tiempo real (marcadores de microlesión: factor de crecimiento similar a la insulina de tipo 1, factor de crecimiento mecánico e isoformas de cadenas pesadas de miosina [MyHC] embrionaria e isoformas de perinatal; de presencia y activación de células satélite: Pax-7 y m-caderina, respectivamente; y condicionantes del fenotipo fibrilar: MyHC-I, IIa y IIx).

Resultados

Los pacientes tuvieron unas fibras mayores que los sujetos sanos (54 ± 6 frente a 42 ± 4 |a, m2; p < 0,01), con una población de células satélite conservada o ligeramente incrementada (cuantificación ultraestructural: 4,3 ± 1% frente al 3,7 ± 3,5%, p no significativa; Pax-7: 5,5 ± 4,1 frente a 1,6 ± 0,8, unidades arbitrarias [ua], respectivamente, p < 0,05) y una mayor activación (m-caderina: 3,8 ± 2,1 frente a 1,0 ± 1,2 ua; p = 0,05). Esto se asociaba a valores aumentados de marcadores de microlesión (factor de crecimiento similar a la insulina de tipo 1: 0,35 ± 0,34 frente a 0,09 ± 0,08 ua, p < 0,05; factor de crecimiento mecánico: 0,45 ± 0,55 frente a 0,13 ± 0,17 ua, p = 0,05).

Conclusiones

Los músculos intercostales de pacientes con EPOC grave muestran signos indirectos de microlesión, acompañados de la activación de sus células satélite. Esto apunta a la presencia de ciclos continuados de lesión y reparación, lo que podría explicar parcialmente la conservación de sus propiedades estructurales.

Palabras clave:
EPOC
Disfunción muscular
Daño
Reparación
Células satélite
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This study was supported by funds from the European Union (Fifth Framework Programme, reference QLRT-2000-00417), the Spanish Ministry of Science and Technology (National R+D Plan, reference SAF 2001-0426), the Spanish Ministry of Health (Red RESPIRA, reference RTIC C03/11, Health Research Fund, Carlos III Health Institute), the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and the Generalitat de Cataluña (2005SGR01060).

J. Martínez-Llorens was supported by institutional funding from SEPAR, the Catalan Society of Pulmonology (SOCAP), and the Municipal Institute for Medical Research (IMIM, grants for residents, 2002 and 2003).

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