Rationale:
Autophagy can preserve cell viability under conditions of mild ischemic stress by degrading damaged organelles for ATP production, but under conditions of severe ischemia, it can promote cell death and worsen cardiac performance. Mesenchymal stem cells (MSCs) are cardioprotective when tested in animal models of myocardial infarction (MI), but whether these benefits occur through the regulation of autophagy is unknown.
Objective:
To determine whether transplanted MSCs reduce the rate of autophagic degradation (autophagic flux) in infarcted hearts and if so, to characterize the mechanisms involved.
Methods and Results:
Treatment with transplanted MSCs improved cardiac function and infarct size while reducing apoptosis and measures of autophagic flux (BafA1-induced LC3-II accumulation and autophagosome/autolysosome prevalence) in infarcted mouse hearts. In hypoxia and serum deprivation (H/SD)-cultured neonatal mouse cardiomyocytes (NMCMs), autophagic flux and cell death, as well as p53-Bnip3 signaling, declined when the cells were cultured with MSCs or MSCs-secreted exosomes, but the changes associated with MSCs-secreted exosomes (MSCs-exo) were largely abolished by pretreatment with the exosomal inhibitor GW4869. Furthermore, a mimic of the exosomal oligonucleotide miR-125b reduced, while an anti-miR-125b oligonucleotide increased, autophagic flux, cell death, via modulating p53-Bnip3 signaling in H/SD-cultured NMCMs. In the in vivo mouse MI model, MSCs-exo, but not the exosomes obtained from MSCs pretreated with the anti-miR-125b oligonucleotide (MSCs-exoanti-miR-125b), recapitulated the same results as the in vitro experiments. Moreover, measurements of infarct size and cardiac function were significantly better in group that were treated with MSCs-exo than the MSCs-exoanti-miR-125b group.
Conclusions:
The beneficial effects offered by MSCs transplantation after MI are at least partially due to improved autophagic flux through excreted exosome containing mainly miR-125b-5p.
Pharmacology, Toxicology and Pharmaceutical Science
4
3%
Psychology
3
3%
Other
11
9%
Unknown
40
34%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 October 2019.
All research outputs
#6,308,522
of 33,493,714 outputs
Outputs from Circulation Research
#2,524
of 9,110 outputs
Outputs of similar age
#87,748
of 368,021 outputs
Outputs of similar age from Circulation Research
#43
of 97 outputs
Altmetric has tracked 33,493,714 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,110 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.5. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 368,021 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 97 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
