دورية أكاديمية
أعرض في EDS

Prevention of hypovolemic circulatory collapse by IL-6 activated Stat3.

التفاصيل البيبلوغرافية
العنوان: Prevention of hypovolemic circulatory collapse by IL-6 activated Stat3.
المؤلفون: Jeffrey A Alten, Ana Moran, Anna I Tsimelzon, Mary-Ann A Mastrangelo, Susan G Hilsenbeck, Valeria Poli, David J Tweardy
المصدر: PLoS ONE, Vol 3, Iss 2, p e1605 (2008)
بيانات النشر: Public Library of Science (PLoS), 2008.
سنة النشر: 2008
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT) 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3beta, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC2225503?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0001605
URL الوصول: https://doaj.org/article/db03fc2a50424f1993e33bb1c8e31c4c
رقم الأكسشن: edsdoj.b03fc2a50424f1993e33bb1c8e31c4c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0001605