Dataset Information

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

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 ?TL 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 ?TL were not related to outcomes over long-term follow-up.

SUBMITTER: Teubel I

PROVIDER: S-EPMC5819711 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Teubel Iris I Elchinova Elena E Roura Santiago S Fernández Marco A MA Gálvez-Montón Carolina C Moliner Pedro P de Antonio Marta M Lupón Josep J Bayés-Genís Antoni A

Journal of translational medicine 20180220 1

<h4>Background</h4>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.<h4>Methods</h4>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 c ...[more]

PMID: 29463269

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Project description:AimsThere are limited data examining the role of immune checkpoint (IC) ligands in the pathophysiology of heart failure (HF). Therefore, we explore this in three HF animal models and in three different human cohorts (healthy, stable, and worsening HF).Methods and resultsTranscriptomic analyses of cardiac tissue of three different HF mouse models revealed differentially expressed IC receptors and their ligands compared with control mice. Based on this observation, serum levels of three well-known IC ligands (i.e. sPD-L1, sPD-L2 and galectin-9) were measured in stable HF patients from the Vitamin D Chronic Heart Failure (VitD-CHF) study (n = 101), as well as healthy individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (n = 58). sPD-L1, sPD-L2, and galectin-9 were all associated with New York Heart Association classification. In multivariate linear regression analyses, all three IC ligands were associated with galectin-3 (β = 0.230, β = 0.283, and β = 0.304, respectively). sPD-L1 and galectin-9 were also associated with hs-troponin-T (β = 0.386 and β = 0.314). Regarding prognosis, higher serum levels of sPD-L1 and galectin-9 were significantly associated with increased risk for HF hospitalization and all-cause mortality [hazard ratio 1.69 (1.09-2.59) and hazard ratio 1.50 (1.06-2.12)]. Furthermore, the importance of IC ligands was tested in another stage of HF, namely worsening HF patients. In the worsening HF cohort (The BIOlogy Study to Tailored Treatment in Chronic Heart Failure) (n = 2032), sPD-L2 and galectin-9 were associated with New York Heart Association classification and significantly predicted outcome with an increased relative risk of 15% and 20%, after multivariable adjustment, respectively.ConclusionsIC ligands are expressed in cardiac disease models, and serum levels of IC ligands are elevated in HF patients, are associated with disease severity, and significantly predict prognosis. These data indicate a potential role for IC ligands in HF pathogenesis.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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