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Tachycardia pacing induces myocardial neovascularization and mobilizes circulating endothelial progenitor cells partly via SDF-1 pathway in canines

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Abstract

Neovascularization plays pivotal role in ischemic heart failure; however, it is unclear in non-ischemic heart failure. Non-ischemic heart failure was induced by chronic rapid right ventricular pacing at 200 beats/min, respectively, for 3 and 6 weeks in 12 dogs. Sham-operation was performed in another 6 dogs as control. Three-week tachycardia pacing could induce mild/moderate heart failure and 6-week pacing could induce severe heart failure. Pan-microvessel density (MVD) was assessed by CD31 and neovascularization density was assessed by CD105. Mean CD31-MVD and CD105-MVD were significantly increased after 3-week pacing. However, CD105-MVD was significantly decreased by 80 % in 6-week pacing group compared with 3-week pacing group, whereas CD31-MVD was only decreased slightly (15 %; P < 0.05). Myocardial proangiogenic factor stromal cell-derived factor 1 (SDF-1), hypoxia-inducible factors 1α (HIF-1α, a transcription factor which could regulate SDF-1 expression), serum SDF-1 levels and circulating EPC mobilization were greatly elevated after 3-week pacing but nearly returned to baseline level after 6-week pacing, which were in accordance with the changes of neovascularization levels assessed by CD105. Angiogenesis and migrating ability of EPCs were enhanced after stimulation of SDF-1, which could be abolished by pretreatment with SDF-1 receptor antagonist AMD3100. In addition, angiogenesis and migrating functions of EPCs were significantly enhanced by the serum from 3-week pacing dogs, but had much weaker response to the serum from 6-week pacing dogs. In conclusion, tachycardia pacing-induced non-ischemic heart failure, promoted myocardial neovascularization and mobilized circulating EPCs, which might be mediated partly through SDF-1 pathway.

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China (No. 81100101 and No. 81270212), Program for New Century Excellent Talents in University (NCET-13-0606), and Guangdong Province Natural Science Fund (Nos. S2013010014011 and 10451008901004814).

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The authors declare that they have no conflict of interest.

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Correspondence to YangXin Chen.

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J. Mai, F. Wang and Q. Qiu have contributed equally.

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Mai, J., Wang, F., Qiu, Q. et al. Tachycardia pacing induces myocardial neovascularization and mobilizes circulating endothelial progenitor cells partly via SDF-1 pathway in canines. Heart Vessels 31, 230–240 (2016). https://doi.org/10.1007/s00380-014-0613-5

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  • DOI: https://doi.org/10.1007/s00380-014-0613-5

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