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Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

Telomere attrition in heart failure: a flow-FISH longitudinal analysis of circulating monocytes

Authors: Iris Teubel, Elena Elchinova, Santiago Roura, Marco A. Fernández, Carolina Gálvez-Montón, Pedro Moliner, Marta de Antonio, Josep Lupón, Antoni Bayés-Genís

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

Background

Cross-sectional investigations report shorter telomeres in patients with heart failure (HF); however, no studies describe telomere length (TL) trajectory and its relationship with HF progression. Here we aimed to investigate telomere shortening over time and its relationship to outcomes.

Methods

Our study cohort included 101 ambulatory patients with HF. Blood samples were collected at baseline (n = 101) and at the 1-year follow-up (n = 54). Using flow-FISH analysis of circulating monocytes, we simultaneously measured three monocyte subsets—classical (CD14++CD16), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++)—and their respective TLs based on FITC-labeled PNA probe hybridization. The primary endpoints were all-cause death and the composite of all-cause death or HF-related hospitalization, assessed at 2.3 ± 0.6 years. All statistical analyses were executed by using the SPSS 15.0 software, and included Student’s t test and ANOVA with post hoc Scheffe analysis, Pearson or Spearman rho correlation and univariate Cox regression when applicable.

Results

We found high correlations between TL values of different monocyte subsets: CD14++CD16+ vs. CD14++CD16, R = 0.95, p < 0.001; CD14++CD16+ vs. CD14+CD16++, R = 0.90, p < 0.001; and CD14++CD16 vs. CD14+CD16++, R = 0.89, p < 0.001. Mean monocyte TL exhibited significant attrition from baseline to the 1-year follow-up (11.1 ± 3.3 vs. 8.3 ± 2.1, p < 0.001). TL did not significantly differ between monocyte subsets at either sampling time-point (all p values > 0.1). Cox regression analyses did not indicate that TL or ΔTL was associated with all-cause death or the composite endpoint.

Conclusions

Overall, this longitudinal study demonstrated a ~ 22% reduction of TL in monocytes from ambulatory patients with HF within 1 year. TL and ΔTL were not related to outcomes over long-term follow-up.
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Literature
1.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefPubMed Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefPubMed
2.
3.
go back to reference Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. J Mol Biol. 1992;225:951–60.CrossRefPubMed Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. J Mol Biol. 1992;225:951–60.CrossRefPubMed
5.
go back to reference van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol. 2007;49:1459–64.CrossRefPubMed van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol. 2007;49:1459–64.CrossRefPubMed
6.
go back to reference Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014;14:392–404.CrossRefPubMed Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014;14:392–404.CrossRefPubMed
8.
go back to reference Roura S, Fernández MA, Elchinova E, Teubel I, Requena G, Cabanes R, et al. Brilliant violet fluorochromes in simultaneous multicolor flow cytometry-fluorescence in situ hybridization measurement of monocyte subsets and telomere length in heart failure. Lab Invest. 2016;96:1223–30.CrossRefPubMed Roura S, Fernández MA, Elchinova E, Teubel I, Requena G, Cabanes R, et al. Brilliant violet fluorochromes in simultaneous multicolor flow cytometry-fluorescence in situ hybridization measurement of monocyte subsets and telomere length in heart failure. Lab Invest. 2016;96:1223–30.CrossRefPubMed
9.
go back to reference Zamora E, Lupón J, Vila J, Urrutia A, de Antonio M, Sanz H, et al. Estimated glomerular filtration rate and prognosis in heart failure: value of the MDRD-4, CDK-EPI, and Cockroft-Gault formulas. J Am Coll Cardiol. 2012;59:1709–15.CrossRefPubMed Zamora E, Lupón J, Vila J, Urrutia A, de Antonio M, Sanz H, et al. Estimated glomerular filtration rate and prognosis in heart failure: value of the MDRD-4, CDK-EPI, and Cockroft-Gault formulas. J Am Coll Cardiol. 2012;59:1709–15.CrossRefPubMed
10.
go back to reference Gastelurrutia P, Lupón J, de Antonio M, Urrutia A, Díez C, Coll R, et al. Statins in heart failure: the paradox between large randomized clinical trials and real life. Mayo Clin Proc. 2012;87:555–60.CrossRefPubMedPubMedCentral Gastelurrutia P, Lupón J, de Antonio M, Urrutia A, Díez C, Coll R, et al. Statins in heart failure: the paradox between large randomized clinical trials and real life. Mayo Clin Proc. 2012;87:555–60.CrossRefPubMedPubMedCentral
11.
go back to reference World Medical Association. World medical association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4.CrossRef World Medical Association. World medical association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–4.CrossRef
12.
go back to reference Vindeløv LL, Christensen IJ, Jensen G, Nissen NI. Limits of detection of nuclear DNA abnormalities by flow cytometric DNA analysis. Results obtained by a set of methods for sample-storage, staining and internal standardization. Cytometry. 1983;3:332–9.CrossRefPubMed Vindeløv LL, Christensen IJ, Jensen G, Nissen NI. Limits of detection of nuclear DNA abnormalities by flow cytometric DNA analysis. Results obtained by a set of methods for sample-storage, staining and internal standardization. Cytometry. 1983;3:332–9.CrossRefPubMed
13.
go back to reference Hultdin M, Grönlund E, Norrback K, Eriksson-Lindström E, Just T, Roos G. Telomere analysis by fluorescence in situ hybridization and flow cytometry. Nucleic Acids Res. 1998;26:3651–6.CrossRefPubMedPubMedCentral Hultdin M, Grönlund E, Norrback K, Eriksson-Lindström E, Just T, Roos G. Telomere analysis by fluorescence in situ hybridization and flow cytometry. Nucleic Acids Res. 1998;26:3651–6.CrossRefPubMedPubMedCentral
14.
go back to reference Wand T, Fang M, Chen C, Hardy N, McCoy JP Jr, Dumitriu B, et al. Telomere content measurement in human hematopoietic cells: comparative analysis of qPCR and Flow-FISH techniques. Cytom A. 2016;89:914–21.CrossRef Wand T, Fang M, Chen C, Hardy N, McCoy JP Jr, Dumitriu B, et al. Telomere content measurement in human hematopoietic cells: comparative analysis of qPCR and Flow-FISH techniques. Cytom A. 2016;89:914–21.CrossRef
15.
go back to reference van der Harst P, de Boer RA, Samani NJ, Wong LS, Huzen J, Codd V, et al. Telomere length and outcome in heart failure. Ann Med. 2010;42:36–44.CrossRefPubMed van der Harst P, de Boer RA, Samani NJ, Wong LS, Huzen J, Codd V, et al. Telomere length and outcome in heart failure. Ann Med. 2010;42:36–44.CrossRefPubMed
16.
go back to reference van der Harst P, Wong LS, de Boer RA, Brouilette SW, van der Steege G, Voors AA, et al. Possible association between telomere length and renal dysfunction in patients with chronic heart failure. Am J Cardiol. 2008;102:207–10.CrossRefPubMed van der Harst P, Wong LS, de Boer RA, Brouilette SW, van der Steege G, Voors AA, et al. Possible association between telomere length and renal dysfunction in patients with chronic heart failure. Am J Cardiol. 2008;102:207–10.CrossRefPubMed
17.
go back to reference Wong LS, van der Harst P, de Boer RA, Codd V, Huzen J, Samani NJ, et al. Renal dysfunction is associated with shorter telomere length in patients with heart failure. Clin Res Cardiol. 2008;98:629–34.CrossRef Wong LS, van der Harst P, de Boer RA, Codd V, Huzen J, Samani NJ, et al. Renal dysfunction is associated with shorter telomere length in patients with heart failure. Clin Res Cardiol. 2008;98:629–34.CrossRef
18.
go back to reference Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffet GE, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci USA. 2003;100:5378–83.CrossRefPubMedPubMedCentral Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffet GE, et al. Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci USA. 2003;100:5378–83.CrossRefPubMedPubMedCentral
19.
go back to reference Masi S, D’Aiuto F, Martin-Ruiz C, Kahn T, Wong A, Ghosh AK, et al. Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort. Eur Heart J. 2014;35:3296–303.CrossRefPubMedPubMedCentral Masi S, D’Aiuto F, Martin-Ruiz C, Kahn T, Wong A, Ghosh AK, et al. Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort. Eur Heart J. 2014;35:3296–303.CrossRefPubMedPubMedCentral
20.
go back to reference Zhang N, Tse G, Liang X, Li G, Liu T. Telomere length: a newly marker for predicting atrial fibrillation? Int J Cardiol. 2017;239:21.CrossRefPubMed Zhang N, Tse G, Liang X, Li G, Liu T. Telomere length: a newly marker for predicting atrial fibrillation? Int J Cardiol. 2017;239:21.CrossRefPubMed
21.
go back to reference Roberts JD, Dewland TA, Longoria J, Fitzpatrick AL, Ziv E, Hu D, et al. Telomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging. Circ Arrhythm Electrophysiol. 2014;7:1026–32.CrossRefPubMedPubMedCentral Roberts JD, Dewland TA, Longoria J, Fitzpatrick AL, Ziv E, Hu D, et al. Telomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging. Circ Arrhythm Electrophysiol. 2014;7:1026–32.CrossRefPubMedPubMedCentral
22.
go back to reference Carlquist JF, Knight S, Cawthon RM, Le VT, Jared Bunch T, Horne BD, et al. Shortened telomere length is associated with paroxysmal atrial fibrillation among cardiovascular patients enrolled in the Intermountain Heart Collaborative Study. Heart Rhythm. 2016;13:21–7.CrossRefPubMed Carlquist JF, Knight S, Cawthon RM, Le VT, Jared Bunch T, Horne BD, et al. Shortened telomere length is associated with paroxysmal atrial fibrillation among cardiovascular patients enrolled in the Intermountain Heart Collaborative Study. Heart Rhythm. 2016;13:21–7.CrossRefPubMed
Metadata
Title
Telomere attrition in heart failure: a flow-FISH longitudinal analysis of circulating monocytes
Authors
Iris Teubel
Elena Elchinova
Santiago Roura
Marco A. Fernández
Carolina Gálvez-Montón
Pedro Moliner
Marta de Antonio
Josep Lupón
Antoni Bayés-Genís
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1412-z

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