fig4

STEMIN and YAP5SA synthetic modified mRNAs regenerate and repair infarcted mouse hearts

Figure 4. Injections of the combination of STEMIN and YAP5SA mmRNA repaired infarcted adult mouse hearts in vivo. (A) Schematic diagram of long-term in vivo experiments in adult mice (100 days old) infarcted by LAD ligation. Five equal injections of STEMIN (50 µg in 38 µL) and YAP5SA (50 µg in 22 µL) with 33 µL Lipofectamine MessengerMAX around the cardiac infarct. In addition, Individual synthetic mmRNA were tested for their ability to restore cardiac function following infarctions. The control group was injected with PBS (60 µL) with 33 µL Lipofectamine MessengerMAX. Echo Doppler measurements were taken prior to infarction and one, two, and four weeks after mmRNA injections. (B) Cardiac function was graphed for Echo Doppler measurements of the infarcted controls (six mice) and the combination of STEMIN and YAP5SA mmRNA experimental group (four mice) from the same inbred liter. The EF declined greater for the control than the combination experimental group by the second and fourth weeks, and both were significantly different (P < 0.05, two-tailed, shown by *). EF of STEMIN or YAP5SA mmRNA individual injections into infarcted hearts failed to significantly improve cardiac EF above the control levels. STEMIN showed a slight trend upwards and YAP5SA was not better than the infarcted controls. (C) At the end of four weeks, the hearts were removed, sectioned, and stained with Picrosirius red. The infarct zone was marked as pink/red with the Picrosirius staining. (D) Infarct scar area and total area of myocardium were traced and measured by ImageJ. Infarcted size% = Picroirius red + scar area/total ventricular area. Measurements of the infarct zone taken from the combination of STEMIN and YAP5SA mmRNA experimental group injected treatment group (four hearts) compared to all controls (six hearts) showed significant reduction (P < 0.05, two-tailed, shown by *). STEMIN injections alone tended to reduce the size of the cardiac infarcts stained by Picrosirius red but were statistically insignificant. YAP5SA mmRNA was not better than STEMIN in cardiac repair.

The Journal of Cardiovascular Aging

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