Hypoxia-preconditioned mesenchymal stem cell-derived exosomes attenuate myocardial ischemia/reperfusion injury by miR-29b-3p via PINK1/Parkin-mediated mitophagy

Figure 2 Exosome therapy can improve myocardial ischemia/reperfusion injury in mice. A: Schematic diagram of intramyocardial injection of exosome (Exo) and hypoxia-preconditioned mesenchymal stem cell-derived Exo (HPC-Exo) in the ischemia/reperfusion (I/R) mouse model; B: Evans blue and triphenyltetrazolium chloride double staining of hearts 28 days after different treatments. Blue represents non-ischemic areas. Red represents ischemic areas. White represents infarcted areas (n = 6); C and D: Echocardiographic measurements of left ventricular end-diastolic diameter, left ventricular end-systolic diameter, ejection fraction, and fractional shortening in mice subjected to sham surgery, I/R, Exo treatment, and HPC-Exo treatment from 2 days to 4 weeks post-myocardial I/R injury (n = 8); E and F: Representative fluorescent micrographs of cardiomyocyte apoptosis (E) and quantitative analysis of apoptosis rates (F); G: Schematic diagram of co-incubation of Exo and HPC-Exo with cardiomyocytes (n = 3); H: Dihydroethidium staining of myocardial cells; I and J: Flow cytometric analysis of dihydroethidium-stained myocardial cells (I) and quantitative analysis of oxidative stress in myocardial cells (J); K and L: Representative flow cytometry plots showing quantitative analysis of the apoptosis rate (K) and the effects of different treatments on cell apoptosis (L). ^aP < 0.05, ^bP < 0.01, ^cP < 0.001, ^dP < 0.0001. Con: Control; DAPI: 4’,6-diamidino-2-phenylindole; DHE: Dihydroethidium; Exo: Normoxic exosomes; HPC-Exo: Hypoxia-preconditioned mesenchymal stem cells-derived exosomes; H/R: Hypoxia/reperfusion; I/R: Ischemia/reperfusion; LVEDd: Left ventricular end-diastolic diameter; LVESd: Left ventricular end-systolic diameter; MFI: Mean fluorescent intensity; PI: Propidium iodide; TUNEL: Transferase dUTP nick end labeling.