TOLLIP adenovirus

Numerous studies have shown that microRNA (miR) modification onto MSCs prevents cell death or autophagy, thereby limiting the size of MI and improving myocardial repair in MI tissue. miRs are considered reliable biomarkers of MI because they regulate downstream genes or axes and affect myocardial function. miR-324 is downregulated in hypoxia/reoxygenation-induced injured cardiomyocytes and inhibits cell proliferation. Here, it was shown that adipose-derived stem cell (ADSC) transplantation modestly enhanced cardiac function in MI rats, reduced enzyme levels, and reduced infarct size and apoptosis; whereas miR-324-5p-modified ADSCs could better promote repair after MI. Mechanistically, miR-324-5p targets TOLLIP in myocardial tissue. Furthermore, TOLLIP overexpression attenuated the promoting effect of miR-324-5p-modified ADSCs in repair after myocardial infarction (MI) in rats. These results suggest that miR-324-5p-modified ADSCs significantly enhance myocardial repair after MI by targeting TOLLIP in myocardial tissue.

To confirm that miR-324-5p-modified ADSCs promote myocardial repair by targeting TOLLIP in myocardial tissue, the researchers conducted a functional rescue experiment. By injecting adenovirus (Ad)-TOLLIP into the miR-ADSCs group rats, the expression of TOLLIP in myocardial tissue was successfully upregulated (Figure 1A). The results showed that the myocardial function of MI rats was weakened (Figure 1B), and the levels of cTnT and CK-MB in serum were increased (Figure 1C). In addition, after overexpression of TOLLIP, the degree of MI and apoptotic cells in the myocardial tissue of MI rats were significantly increased (Figures 1D and 1E). These results indicate that TOLLIP overexpression disrupts the promoting effect of miR-324-5p-modified ADSCs in post-MI repair in rats.

Figure 1. TOLLIP overexpression spoils the promotive role of miR-324-5p-modified ADSCs in post-MI repair in rats. (Ji Z, et al., 2021)