Mobilization of bone marrow-derived Nkx2-5(+) cardiac progenitor cells under condition of acute myocardial ischemia.
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.
Dong
Hong-Yan
HY
Department of Cardiothoracic Surgery, Xuzhou Medical College, Xuzhou, China.
Xu
Zhi-Wei
ZW
Zhang
Zhong-Ming
ZM
Yu
Hong-Li
HL
Xu
Xia-Hong
XH
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D019650:Hematopoietic Stem Cell Mobilization; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors