RNAi-Mediated Down-Regulation of CD47 Protects against Ischemia/Reperfusion-Induced Myocardial Damage via Activation of eNOS in a Rat Model
| العنوان: | RNAi-Mediated Down-Regulation of CD47 Protects against Ischemia/Reperfusion-Induced Myocardial Damage via Activation of eNOS in a Rat Model |
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| المؤلفون: | Jun Yang, Song Li, Lihua Chen, Jiawang Ding, Zhi-xin Fan, Jian Yang, Chaojun Yang, Huibo Wang, Xiao-wen Liu |
| المصدر: | Cellular Physiology and Biochemistry, Vol 40, Iss 5, Pp 1163-1174 (2016) |
| بيانات النشر: | S. Karger AG, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Nitric Oxide Synthase Type III, Physiology, Green Fluorescent Proteins, Ischemia, Down-Regulation, CD47 Antigen, Myocardial Reperfusion Injury, Ischemia/reperfusion injury, Pharmacology, Nitric Oxide, Transfection, Creatine, medicine.disease_cause, lcsh:Physiology, Adenoviridae, Nitric oxide, lcsh:Biochemistry, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Enos, Lactate dehydrogenase, medicine, Animals, lcsh:QD415-436, CD47, lcsh:QP1-981, biology, business.industry, Myocardium, medicine.disease, biology.organism_classification, Up-Regulation, Enzyme Activation, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Heart failure, biology.protein, Endothelial nitric oxide synthase, RNA Interference, Creatine kinase, business, Oxidative stress |
| الوصف: | Background/Aims: Oxidative stress is strongly implicated in the pathogenesis of myocardial damage caused by ischemia reperfusion (I/R). Previous studies have confirmed that cardiac CD47 drives left ventricular heart failure. However, the role for CD47 in myocardial I/R injury (MIRI) has not previously been proposed. This study was designed to investigate whether down-regulation of CD47 using RNA interference (RNAi) technology can relieve inhibition of nitric oxide signaling and attenuate myocardial damage in a rat model of I/R. Methods: Male Sprague-Dawley rats (n = 40) were randomly allocated to four groups and pre-treated either with saline (Sham and I/R groups), or adenovirus expressing either control (Ad-EGFP-N) or CD47-targeting (Ad-EGFP-CD47) RNAi. After four days, the rat MIRI model was established by occluding the left anterior descending coronary artery for 30 min, followed by reperfusion for 3 h. Heart tissue was harvested and assessed by immunohistochemistry, western blot, and quantitative RT-PCR. Outcome measures included infarct size, myocardial enzyme (creatine kinase, creatine kinase-MB, and lactate dehydrogenase) levels in serum, markers of oxidative stress, and morphological changes to the myocardium. Results: Delivery of Ad-EGFP-CD47 RNAi into the myocardium remarkably decreased CD47 expression levels. Down-regulation of CD47 was significantly associated with reduced infarct size and serum levels of myocardial enzymes, increased activity of endothelial nitric oxide synthase, increased levels of nitric oxide, and decreased levels of oxidative stress. Conclusion: These data indicate that down-regulation of CD47 exerts a protective effect against MIRI, which may be attributable to attenuation of oxidative stress via activation of the eNOS/NO signaling pathway. |
| تدمد: | 1421-9778 1015-8987 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::830581f273285bf34a9b86c7d42702baTest https://doi.org/10.1159/000453170Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....830581f273285bf34a9b86c7d42702ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14219778 10158987 |
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