Abstract 424: Knockdown of Nerve Growth Factor in Spinal Cord Reduces Myocardial Reperfusion Injury by Suppressing Ischemic Nociceptive Signaling Transmission
| العنوان: | Abstract 424: Knockdown of Nerve Growth Factor in Spinal Cord Reduces Myocardial Reperfusion Injury by Suppressing Ischemic Nociceptive Signaling Transmission |
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| المؤلفون: | Zhenxiao Ma, Ye Zhang, Shufang He, Mengyun Dou |
| المصدر: | Circulation Research. 123 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Cardioprotection, Gene knockdown, Physiology, business.industry, Central nervous system, Myocardial Reperfusion Injury, Pharmacology, Spinal cord, medicine.anatomical_structure, Nociception, Nerve growth factor, nervous system, Afferent, medicine, Cardiology and Cardiovascular Medicine, business |
| الوصف: | Objective: To test the hypothesis that nerve growth factor (NGF) sensitized spinal cardiac afferent activity contributes to myocardial ischemia-reperfusion injury (IRI). Methods and Results: The expression levels of NGF were increased in both dorsal root ganglion (DRG) and spinal cord after myocardial IRI in rats. Whole-cell patch clamp in cultured DRG neurons revealed that NGF aggravated capsaicin-induced current which was eliminated by the transient receptor potential vanilloid 1 (TRPV1) antagonist. Intrathecal injection of lentivirus-mediated NGF shRNA into thoracic T1-T8 segments successfully suppressed NGF mRNA and protein levels. Knockdown of NGF in spinal cord significantly limited IRI-induced infarct size, lowered down the concentration of cardiac troponin I (cTnI), and improved arrhythmia score. NGF gene suppression markedly reduced IRI-caused elevation of NGF and its receptor tropomyosin receptor kinase A (TrkA), TRPV1 and phosphorylated TRPV1. The activation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) was also inhibited by NGF shRNA. Upon immunofluorescence staining, substance P (SP) and calcitonin gene-related peptide (CGRP) were found strongly stained in DRG and spinal dorsal horn following myocardial IRI, while these immunoreactive staining were repressed due to NGF gene knockdown. Conclusions: NGF aggravated spinal cardiac afferent nerves activity by sensitizing TRPV1-mediated nociceptive signal transmission. Inhibition of spinal NGF expression effectively protected the heart from myocardial IRI, which may imply a new potential therapeutic approach in ischemic heart diseases. |
| تدمد: | 1524-4571 0009-7330 |
| DOI: | 10.1161/res.123.suppl_1.424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c37f1e45c6f510255a70fedf32c0fef1 https://doi.org/10.1161/res.123.suppl_1.424 |
| رقم الانضمام: | edsair.doi...........c37f1e45c6f510255a70fedf32c0fef1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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| DOI: | 10.1161/res.123.suppl_1.424 |