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Telomere attrition in heart failure: a flow-FISH longitudinal analysis of circulating monocytes
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....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819711/ https://www.ncbi.nlm.nih.gov/pubmed/29463269 http://dx.doi.org/10.1186/s12967-018-1412-z |
Sumario: | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1412-z) contains supplementary material, which is available to authorized users. |
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