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Mobilization of bone marrow-derived Nkx2-5+ cardiac progenitor cells undercondition of acute myocardial ischemia

DONG Hong-Yan, XU Zhi-Wei, ZHANG Zhong-Ming, YU Hong-Li, XU Xia-Hong

Center of Neurobiological Research； Department of Cardiothoracic Surgery of Affiliated Hospital, Xuzhou Medical College, Xuzhou 221002, China

Abstract

The present study aimed to observe the morphological distribution of bone marrow (BM)-derived Nkx2-5+ cardiac progenitor cells (CPCs) in bone marrow niche and evaluate the effect of acute myocardial ischemia (AMI) on the mobilizion of BM-derived Nkx2-5+ CPCs. Animal models of BALB/c mouse AMI, cerebral and hind-limb ischemia were established. Nanogold labeling method, immunofluorescence and Western blot were used to identify the distribution of BM-derived Nkx2-5+ CPCs and the expressions of Nkx2-5 protein in peripheral blood and BM after AMI. Meanwhile, in different ischemia organ models and after AMD3100 (SDF-1/ CXCR4 antagonist) pretreatment in AMI model, Nkx2-5 protein expressions in peripheral blood were also assayed. Nkx2-5+ CPCs were found to locate in cavitas medullaris. The percentage of Nkx2-5+ CPCs in blood increased immediately after AMI. Nkx2-5 protein expression in peripheral blood was also upregulated at the timepoint of 24 h post-AMI (P<0.01) and kept stable without further enhancement from day 1 to day 7 post-AMI. In BM, Nkx2-5 protein expression was upregulated immediately after AMI and downregulated afterwards (P<0.01). After AMD3100 pretreatment in AMI group, Nkx2-5 protein expression was significantly inhibited in peripheral blood (P<0.05). In cerebral and hind-limb ischemia models, Nkx2-5 protein expressions were significantly lower than that in AMI group (P<0.01), but with no significant difference to control group. These results suggest that Nkx2-5+ CPCs are physiologically resident in BM and AMI initiates mobilization of BM-derived Nkx2-5+ CPCs in a predominant organ-specific manner. In the procedure of mobilization, SDF-1 may play a critical role in a chemoattracted manner.

Key words: cardiac progenitor cells; bone marrow; Nkx2-5; mobilization; myocardial ischemia

Received: 2008-12-03　　Accepted: 2009-02-19

Corresponding author: 张中明　　E-mail: zhang_zhongming@yahoo.com.cn

Citing This Article：

DONG Hong-Yan, XU Zhi-Wei, ZHANG Zhong-Ming, YU Hong-Li, XU Xia-Hong. Mobilization of bone marrow-derived Nkx2-5+ cardiac progenitor cells undercondition of acute myocardial ischemia. Acta Physiol Sin 2009; 61 (2): 185-193 (in Chinese with English abstract).