Mobilization of bone marrow-derived Nkx2-5(+) cardiac progenitor cells under condition of acute myocardial ischemia.
- Author:
Hong-Yan DONG
1
;
Zhi-Wei XU
;
Zhong-Ming ZHANG
;
Hong-Li YU
;
Xia-Hong XU
Author Information
1. Department of Cardiothoracic Surgery, Xuzhou Medical College, Xuzhou, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Marrow;
metabolism;
Hematopoietic Stem Cell Mobilization;
Homeobox Protein Nkx-2.5;
Homeodomain Proteins;
metabolism;
Mice;
Mice, Inbred BALB C;
Myocardial Infarction;
metabolism;
Myocardium;
cytology;
Stem Cells;
cytology;
Transcription Factors;
metabolism
- From:
Acta Physiologica Sinica
2009;61(2):185-193
- CountryChina
- Language:English
-
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.
