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LSC Abstract – Increased oxidative stress leads to telomere shortening in children with alpha-1 antitrypsin deficiency

Sara Pastor, Amparo Escribano, Silvia Castillo, Ana Reula, María Mercedes Navarro-García, Francisco Sanz, Estrella Fernandez-Fabrellas, Pilar Codoñer-Franch, Francisco Jose Dasi Fernandez
European Respiratory Journal 2016 48: PP115; DOI: 10.1183/13993003.congress-2016.PP115
Sara Pastor
1UCIM, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
3Physiology, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
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Amparo Escribano
1UCIM, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
2Paediatrics, Obstetrics and Gynecology, University of Valencia. School of Medicine, Valencia, Spain
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Silvia Castillo
1UCIM, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
2Paediatrics, Obstetrics and Gynecology, University of Valencia. School of Medicine, Valencia, Spain
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Ana Reula
1UCIM, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
3Physiology, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
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María Mercedes Navarro-García
5Surgery, University of Valencia. School of Medicine, Valencia, Spain
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Francisco Sanz
4Pulmonology, Fundación Investigación Hospital General Valencia, Valencia, Spain
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Estrella Fernandez-Fabrellas
4Pulmonology, Fundación Investigación Hospital General Valencia, Valencia, Spain
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Pilar Codoñer-Franch
1UCIM, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
2Paediatrics, Obstetrics and Gynecology, University of Valencia. School of Medicine, Valencia, Spain
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Francisco Jose Dasi Fernandez
1UCIM, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
3Physiology, Fundación Investigación Hospital Clínico Valencia/IIS INCLIVA, Valencia, Spain
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Abstract

Background: Oxidative stress (OS) is involved in the pathophysiology of AATD (Escribano A. et al. Thorax 2015; 70:82-3). In addition, it has been shown that OS accelerates telomere shortening which is associated to higher emphysema risk in COPD patients.

Rationale and aims: Since AATD is characterised by chronic OS, we hypothesise that telomere shortening would be accelerated in AATD patients and would be associated with higher risk of developing lung disease. This study is aimed to assess the OS profile, the enzymatic antioxidant defence mechanisms and telomere length (TL) in children with AATD and to study its association with AAT phenotypes.

Methods: OS parameters, the activity of the main antioxidant enzymes and TL were prospectively measured in fifty-one children diagnosed with alpha-1 antitrypsin deficiency and thirty-eight control individuals.

Results: AATD patients showed higher GSSG/GSH ratio (p=0.001; p<0.0001, respectively), malondialdehyde (p=0.004; p<0.0001), 8-OHdG (p<0.0001; p<0.0001) and oxidized proteins (p=0.01; p=0.002) than the control group, while total (p<0.0001; p<0.0001) and reduced glutathione levels (p <0.0001; p<0.0001) were decreased. Catalase activity was decreased (p=0.003; p<0.001) leading to the accumulation of H2O2 (p=0.04; p=0.001), which would explain the high levels of OS observed. TL is decreased in patients with AATD compared to control subjects (p<0.001).

Conclusions: Increased OS lead to accelerated telomere shortening in AATD patients. An association between OS, TL and risk of developing lung/liver disease is observed.

Funding: SEPAR 2013 and ISCIII (PI14/02162) grants.

  • Copyright ©the authors 2016
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LSC Abstract – Increased oxidative stress leads to telomere shortening in children with alpha-1 antitrypsin deficiency
Sara Pastor, Amparo Escribano, Silvia Castillo, Ana Reula, María Mercedes Navarro-García, Francisco Sanz, Estrella Fernandez-Fabrellas, Pilar Codoñer-Franch, Francisco Jose Dasi Fernandez
European Respiratory Journal Sep 2016, 48 (suppl 60) PP115; DOI: 10.1183/13993003.congress-2016.PP115

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LSC Abstract – Increased oxidative stress leads to telomere shortening in children with alpha-1 antitrypsin deficiency
Sara Pastor, Amparo Escribano, Silvia Castillo, Ana Reula, María Mercedes Navarro-García, Francisco Sanz, Estrella Fernandez-Fabrellas, Pilar Codoñer-Franch, Francisco Jose Dasi Fernandez
European Respiratory Journal Sep 2016, 48 (suppl 60) PP115; DOI: 10.1183/13993003.congress-2016.PP115
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