Abstract 18383: Circulating Exosomal miR-1a is Markedly Induced by Myocardial Infarction and Downregulates CXCR4 Expression in the Bone Marrow Mononuclear Cells
Rationale: The level of miR-1a in the blood of patients with myocardial infarction (MI) is markedly elevated; however, whether the circulating miR-1 impacts on remote organs has not been studied. Because it is known that MI leads to mobilization of various bone marrow (BM) cells, and that microRNAs are often carried in exosomes, we hypothesize that the MI-induced miR-1 is associated with exosomes and mediates a functional crosstalk between the ischemic heart and the BM.
Methods and Results: We isolated plasma exosomes 12 h after induction of MI in mice and analyzed the exosomal miR-1a by qRT-PCR. The level of circulating exosomal miR-1a was 68 fold higher (p<0.01) in MI group than in Sham-operated group. Additionally, we found a greater amount of miR-1a in the BM mononuclear cells (MNCs) isolated from the MI mice. After MI surgery, the level of miR-1a in the BM MNCs peaked at day 2 (5.7 fold vs. baseline, p<0.05), declined at day 3 (1.7 fold, p0.05). To test whether exosomes mediate transfer of miR-1a into BM MNCs, exosomes isolated from the plasma of MI mice were labeled fluorescently with PKH67, co-cultured with BM MNCs for 4 h, and then analyzed microscopically. We confirmed that the exosomes were internalized in the BM MNCs, which was associated with a significantly greater amount of miR-1a in these cells (3.1 fold, p<0.05). To gain insights into the functional significance of the miR-1a transfer, we transduced a mimic miR-1a into BM MNCs, and analyzed the expression of adhesion molecules and chemokine receptors by serial Western blotting. Notably, we found a significant down-regulation of CXCR4 proteins in these cells (p<0.05), which was confirmed by flow cytometry indicating a decline (by 12.5%, p<0.05) in CXCR4-positive BM MNCs.
Conclusion: Circulating exosomal miR-1a suppresses CXCR4 expression in BM MNCs and may contribute to the BM-cell mobilization during ischemic injury.
Author Disclosures: M. Cheng: None. X. Zhao: None. B. Wu: None. X. Mao: None. G. Yi: None. Q. Zeng: None. G. Qin: None.
- © 2014 by American Heart Association, Inc.