Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.
10.1007/s11655-023-3647-7
- Author:
Si-Nai LI
1
;
Zi-Hao LIU
1
;
Ming-Xue ZHOU
1
;
Wei-Hong LIU
1
;
Xiao-Lei LAI
1
;
Ping LI
1
;
Lei ZHANG
1
;
Ju-Ju SHANG
1
;
Sheng-Lei QIU
1
;
Yan LOU
1
;
Yu-Pei TAN
1
;
Wen-Long XING
1
;
Hong-Xu LIU
2
Author Information
1. Department of Cardiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
2. Department of Cardiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China. lhx_@263.net.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
Danhong Injection;
Exosome;
apoptosis;
miR-125b;
myocardial infarction
- MeSH:
Mice;
Animals;
Tumor Suppressor Protein p53/metabolism*;
Endothelial Cells/metabolism*;
Exosomes/metabolism*;
bcl-2-Associated X Protein/metabolism*;
Myocardium/metabolism*;
Myocardial Infarction/drug therapy*;
Apoptosis;
MicroRNAs/metabolism*
- From:
Chinese journal of integrative medicine
2023;29(12):1099-1110
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.
METHODS:A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.
RESULTS:DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).
CONCLUSION:DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
