Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
PLoS One. 2011;6(8):e23118. doi: 10.1371/journal.pone.0023118. Epub 2011 Aug 18.
We aimed to find support for the hypothesis that telomere length (TL) is causally involved in the pathogenesis of ischemic heart failure (IHF). We measured TL in IHF patients and their high-risk offspring and determined whether mean leukocyte TL reflects TL in CD34+ progenitor. We additionally measured TL of offspring of patients and controls to examine heritability throughout different cell types.
TL was measured by qPCR in overall leukocytes, CD34+ progenitor cells, mononuclear cells (MNCs), and buccal cells in 27 IHF patients, 24 healthy controls and 60 offspring. TL in IHF patients was shorter than healthy controls in leukocytes (p = 0.002), but not in CD34+ cells (p = 0.39), MNCs (p = 0.31) or buccal cells (p = 0.19). Offspring of IHF patients had shorter TL in leukocytes than offspring of healthy subjects (p = 0.04) but not in other cell types. Controls and offspring showed a good within person correlation between leukocytes and CD34+ cells (r 0.562; p = 0.004 and r 0.602; p = 0.001, respectively). In IHF patients and offspring the correlation among cell types was blunted. Finally, we found strong correlations between parent and offspring TL in all four cell types.
Reduced leukocyte TL in offspring of IHF subjects suggests a potential causal link of TL in ischemic heart disease. However, this causality is unlikely to originate from exhaustion of TL in CD34+ progenitor or MNC cells as their lengths are not well captured by overall leukocyte TL. Additionally, we found strong correlations between parent and offspring TL in all examined cell types, suggesting high heritability of TL among cell types.
我们旨在寻找端粒长度（TL）在缺血性心力衰竭（IHF）发病机制中起因果作用的证据。我们测量了 IHF 患者及其高危后代的 TL，并确定白细胞平均 TL 是否反映 CD34+祖细胞中的 TL。我们还测量了患者和对照组后代的 TL，以检查不同细胞类型中 TL 的遗传性。
通过 qPCR 测量了 27 名 IHF 患者、24 名健康对照者和 60 名后代的整体白细胞、CD34+祖细胞、单核细胞（MNC）和口腔细胞中的 TL。与健康对照组相比，IHF 患者的白细胞 TL 较短（p = 0.002），但 CD34+细胞（p = 0.39）、MNC（p = 0.31）或口腔细胞（p = 0.19）中则无差异。与健康对照组的后代相比，IHF 患者的后代白细胞 TL 较短（p = 0.04），但在其他细胞类型中则无差异。对照者和后代之间的白细胞和 CD34+细胞之间具有良好的个体内相关性（r 0.562；p = 0.004 和 r 0.602；p = 0.001）。在 IHF 患者和后代中，细胞类型之间的相关性减弱。最后，我们发现所有四种细胞类型中父母和子女的 TL 之间存在很强的相关性。
IHF 受试者后代的白细胞 TL 降低提示 TL 在缺血性心脏病中存在潜在的因果关系。然而，这种因果关系不太可能源自 CD34+祖细胞或 MNC 细胞中的 TL 耗尽，因为它们的长度无法通过整体白细胞 TL 很好地捕捉到。此外，我们在所有检查的细胞类型中发现了父母和子女 TL 之间的强相关性，表明 TL 在细胞类型中具有很高的遗传性。
