Abstract 220: Adipocyte-Derived Exosome-Containing miRNAs Exacerbated Cardiac Ischemia/Reperfusion Injury in Diabetic Mice
Gan, L; Xie, D; Zhao, D; Gao, E; Koch, WJ; Wang, Y; Ma, X
Published in: Circulation Research
Diabetes significantly exacerbates myocardial ischemia/reperfusion (MI/R) injury. However, the molecules mediate the crosstalk between adipose tissue and heart is unclear. The current study investigated whether exosomes released by adipose tissue, the primary source for circulating exosomes, are responsible for aggravating myocardial ischemia/reperfusion injury in diabetic mice.
6-8 week-old male C57B6/J mice were fed with normal diet (ND) or high fat diet (HFD) for 12 weeks to induce diabetes (characterized by abnormal glucose tolerance and insulin resistance). Exosomes were purified from ND or HFD murine serum and from culture medium of ND or HFD primary adipocytes. Equal amount of exosomes were intramyocardially injected to non-diabetic mice prior to MI/R. Myocardial functional assay showed that the exosomes purified from ND serum and culture medium of ND primary adipocytes attenuates MI/R injury (p<0.05 vs. MI/R). In contrary, the exosomes from HFD serum and culture medium of HFD primary adipocytes markedly depressed cardiac function, enlarged myocardial infarction size and increased cardiomyocyte apoptosis (p<0.05 vs. MI/R). To identify the specific molecules in exosomes that mediate cardiac injury, we performed Venn diagraph assay via combining the two databases (the adipocyte relevant miRNAs; serum exosomal miRNAs sequencing database in diabetic and nondiabetic mice). Candidate miRNAs were selected and validated. RT-qPCR assay confirmed that miR-17-3p, miR-127b-3p, miR-130b-3p, miR-345-5p and miR-532-5p were significantly elevated in exosomes isolated from HFD serum and culture medium of HFD primary adipocytes. Most importantly, these miRNAs were markedly elevated in heart tissue when exosomes isolated from HFD mice serum and culture medium of HFD primary adipocyte were injected.
Our finding suggests that adipose-derived and exosome-carrying miRNAs are the likely molecules mediating the adipocyte-cardiomyocyte communication, thereby aggravating myocardial ischemia/reperfusion injury in diabetic mice.
