Exosome-based WTAP siRNA delivery ameliorates myocardial ischemia-reperfusion injury.
Eur J Pharm Biopharm
; 197: 114218, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38367759
ABSTRACT
Myocardial ischemia/reperfusion (MI/R) injury is the primary cause of postischemicheartfailure. The increased expression of Thioredoxin-interacting protein (TXNIP) has been implicated in MI/R injury, although the detailed mechanism remains incompletely understood. In the present study, we observed the up-regulation of the m6A mRNA methylation complex component Wilms' tumor 1-associating protein (WTAP) in MI/R mice, which led to the m6A modification of TXNIP mRNA and an increase in mRNA abundance. Knock-down of WTAP resulted in a significant reduction in the m6A level of TXNIP mRNA and down-regulated TXNIP expression. Moreover, exosomes engineered with ischemic myocardium-targeting peptide (IMTP) were able to deliver WTAP siRNA into ischemic myocardial tissues, resulting in a specific gene knockdown and myocardial protection. In summary, our findings demonstrate that the WTAP-TXNIP regulatory axis plays a significant role in postischemicheartfailure, and the use of engineered exosomes targeting the ischemic heart shows promise as a strategy for siRNA therapy to protect the heart from injury.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myocardial Reperfusion Injury
/
Exosomes
Limits:
Animals
Language:
En
Journal:
Eur J Pharm Biopharm
Journal subject:
FARMACIA
/
FARMACOLOGIA
Year:
2024
Type:
Article
Affiliation country:
China