Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress

Cells. 2023 Sep 18;12(18):2300. doi: 10.3390/cells12182300.


Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miRSEL). Proteomics demonstrated a highly significant representation of cardiovascular development functions and angiogenesis in CPC exosomes, and RNAseq analysis yielded about 350 different miRNAs; among the exo-miRSEL population, miR-935 was confirmed as the miRNA most significantly up-regulated; interestingly, miR-935 was also found to be preferentially expressed in mouse primary cardiac Bmi1+high CPC, a population highly enriched in progenitors. Furthermore, it was found that transfection of an miR-935 antagomiR combined with oxidative stress treatment provoked a significant increment both in apoptotic and necrotic populations, whereas transfection of a miR-935 mimic did not modify the response. Conclusion. miR-935 is a highly differentially expressed miRNA in exo-miRSEL, and its expression reduction promotes oxidative stress-associated apoptosis. MiR-935, together with other exosomal miRNA members, could counteract oxidative stress-related apoptosis, at least in CPC surroundings.

Keywords: CPC; antagomiR; apoptosis; cardiac progenitor cell; exosome; mi-RNA; miR-935; oxidative stress.

Grants and funding

This work has been funded by grants from the Spanish Ministry of Science and Innovation RTI2018-097604-B-I00 (funded by MCIN/AEI/10.13039/501100011033/ and FEDER) and PID2021-128698OB-I00 (MCIN/AEI/10.13039/501100011033); by the Regional Government of Madrid (S2017/BMD-3692, Avancell), and by the Instituto de Salud Carlos III (RD16/0011/0037) to AB and by the Instituto Salud Carlos III (ISCIII), co-funded by European Regional Development Fund-FEDER (PI19/00501 and PI22/00029), and Gobierno de Navarra (s/n) to BP. JV has been funded by MCIN grant PID2021-122348NB-I00 and Regional Government of Madrid grant P2022/BMD-7333.