Back to Search
Start Over
Egr-1 is involved in coronary microembolization-induced myocardial injury via Bim/Beclin-1 pathway-mediated autophagy inhibition and apoptosis activation
- Source :
- Aging (Albany NY)
- Publication Year :
- 2018
- Publisher :
- Impact Journals, LLC, 2018.
-
Abstract
- Coronary microembolization (CME) substantially reduces the clinical benefits of myocardial reperfusion therapy. Autophagy and apoptosis participate in the pathophysiological processes of almost all cardiovascular diseases, including CME-induced myocardial injury, but the precise underlying mechanisms remain unclear. In the present study, we observed that Egr-1 expression was substantially increased after CME modeling. Inhibition of Egr-1 expression through the targeted delivery of rAAV9-Egr-1-shRNA improved cardiac function and reduced myocardial injury. The microinfarct size was also significantly smaller in the Egr-1 inhibitor group than in the CME group. These benefits were partially reversed by the autophagy inhibitor 3-MA. As shown in our previous study, autophagy in the myocardium was impaired after CME. Inhibition of Egr-1 expression in vivo restored the autophagy flux and reduced myocardial apoptosis, at least partially, by inhibiting the Egr-1/Bim/Beclin-1 pathway, as evidenced by the results of the western blot, RT-qPCR, and TUNEL staining. At the same time, TEM showed a dramatic increase in the number of typical autophagic vacuoles in the Egr-1 inhibitor group compared to the CME group. Based on these findings, the Egr-1/Bim/Beclin-1 pathway may be involved in CME-induced myocardial injury by regulating myocardial autophagy and apoptosis, and this pathway represents a potential therapeutic target in CME.
- Subjects :
- Egr-1
Male
0301 basic medicine
Cardiac function curve
autophagy
Aging
education
Myocardial Infarction
Vacuole
coronary microembolization
Rats, Sprague-Dawley
Random Allocation
03 medical and health sciences
0302 clinical medicine
Western blot
In vivo
Animals
Medicine
myocardial injury
Early Growth Response Protein 1
TUNEL assay
medicine.diagnostic_test
business.industry
Adenine
Autophagy
apoptosis
Cell Biology
Coronary Vessels
Pathophysiology
Rats
Repressor Proteins
body regions
030104 developmental biology
Gene Expression Regulation
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Beclin-1
RNA Interference
business
hormones, hormone substitutes, and hormone antagonists
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....1bf390df03845964081a3ceae93d93eb