Spyridopoulos Ioakim, Erben Young, Brummendorf Tim H, Haendeler Judith, Dietz Klaus, Seeger Florian, Kissel Christine K, Martin Hans, Hoffmann Jedrzej, Assmus Birgit, Zeiher Andreas M, Dimmeler Stefanie
Department of Cardiology, Wolfgang Goethe University of Frankfurt, Germany.
Arterioscler Thromb Vasc Biol. 2008 May;28(5):968-74. doi: 10.1161/ATVBAHA.107.160846. Epub 2008 Feb 14.
We have previously demonstrated that ischemic cardiomyopathy is associated with selective impairment of progenitor cell function in the bone marrow and in the peripheral blood, which may contribute to an unfavorable left ventricular remodeling process.
With this study, we intended to identify the influence of telomere length on bone marrow functionality in 50 patients with coronary artery disease (CAD) and previous myocardial infarction. Mean telomere length (mTL) was measured simultaneously in peripheral blood leukocytes and mononuclear bone marrow cells (BMC), using the flow-FISH method. Telomere erosion already occurred at the bone marrow level, whereby age (39 bp/yr, P=0.025) and the number of affected vessels (434 bp/vessel, P=0.029) were the only independent predictors. Lymphocytes demonstrated significant TL shortening between BMCs and peripheral blood in CAD patients (-1011+/-897 bp) as opposed to an increase in a young control group (+235+/-459 bp, P<0.001). SDF- and VEGF-specific migration of BMCs correlated with mTL of lymphocytes (r=0.42, P<0.001) and was significantly reduced in CAD patients. Finally, the telomere length difference between granulocytes and lymphocytes was the most determinant for telomere-associated bone marrow impairment (P<0.001).
In patients with CAD, telomere shortening of BMCs is dependent on both age and the extent of CAD and correlates with bone marrow cell functionality.
我们先前已证明，缺血性心肌病与骨髓和外周血中祖细胞功能的选择性受损有关，这可能导致不良的左心室重塑过程。
在本研究中，我们旨在确定端粒长度对50例冠心病（CAD）并曾发生心肌梗死患者骨髓功能的影响。使用流式荧光原位杂交（flow-FISH）方法同时测量外周血白细胞和单核骨髓细胞（BMC）中的平均端粒长度（mTL）。端粒侵蚀已在骨髓水平发生，其中年龄（每年39 bp，P = 0.025）和受累血管数量（每支血管434 bp，P = 0.029）是仅有的独立预测因素。与年轻对照组增加（+235±459 bp，P <0.001）相反，CAD患者淋巴细胞在BMC和外周血之间显示出显著的端粒缩短（-1011±897 bp）。BMC的SDF和VEGF特异性迁移与淋巴细胞的mTL相关（r = 0.42，P <0.001），并且在CAD患者中显著降低。最后，粒细胞和淋巴细胞之间的端粒长度差异是端粒相关骨髓损伤的最主要决定因素（P <0.001）。
在CAD患者中，BMC的端粒缩短既取决于年龄，也取决于CAD的程度，并且与骨髓细胞功能相关。
