P3509Leukocyte derived tumour necrosis factor modulates cardiac function in health and disease
| العنوان: | P3509Leukocyte derived tumour necrosis factor modulates cardiac function in health and disease |
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| المؤلفون: | S Walker, G.L. Ackland, A. Gutierrez del Arroyo, Jenifer Sanchez |
| المصدر: | European Heart Journal. 40 |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cardiac function curve, Pathology, medicine.medical_specialty, Necrosis, business.industry, cardiovascular system, medicine, Disease, medicine.symptom, Cardiology and Cardiovascular Medicine, business |
| الوصف: | Purpose Tumour necrosis factor alpha (TNFα) regulates both normal and pathophysiological cardiac function. The regulatory role of TNFα derived from different sources (leukocyte versus cardiac cells) in cardiac physiology is unclear. Deficiency of iRhom2 protein prevents circulating immune cells from shedding TNFα (and CD62L, an adhesion molecule essential for effective immune function). Here we investigated the role of leukocyte derived TNFα in constitutive cardiac function and after cardiac injury. Methods Adult iRhom2-deficient mice (KO) and wildtype (Wt) littermates, of both genders, underwent echocardiography to assess cardiac physiologic function at least 1 week before receiving a single dose of isoproterenol (300mg/kg IP) to induce cellular death in 10% of the cardiomyoctes [1]. Cardiac echocardiography was repeated 36 hours after isoproterenol. Peripheral and cardiac-resident leukocytes were phenotyped by flow cytometry and molecular markers of cardiac stress (atrial and brain natriuretic protein, ANP, BNP) and inflammation (NFkB) were quantified using RT-PCR. Results Peripheral leukocytes from iRhom2 KO mice failed to shed CD62L in response to isoproterenol induced cardiac injury (e.g. neutrophils CD62L Mean Fluorescence Intensity KO: 9149±4616, Wt: 972±558, p Conclusions Inability to shed CD62L and TNFα is associated with constitutive and acquired cardiac dysfunction in iRhom2-deficient mice. These data support the hypothesis that leukocyte-derived TNFα is required for maintaining cardiac function in health and disease. Acknowledgement/Funding National Institute of Academic Anaesthesia/Royal College of Anaesthetists/British Journal of Anaesthesia; National Institute for Health Research |
| تدمد: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehz745.0373 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::1c97f3e2c08b7d63a5fa6c24ba3043f8 https://doi.org/10.1093/eurheartj/ehz745.0373 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........1c97f3e2c08b7d63a5fa6c24ba3043f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15229645 0195668X |
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| DOI: | 10.1093/eurheartj/ehz745.0373 |