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(PP208) Interactions between mast cells and the endothelin system in radiation-induced heart disease.
Boerma, Marjan*,1, Kennedy, Richard2, Kulkarni, Ashwini1, Joseph, Jacob3, Wondergem, Jan4, Wang, Junru1, Hauer-Jensen, Martin1, 1 Departments of Surgery and Pathology, Little Rock, AR, USA2 Loyola University Medical Center, Maywood, IL, USA3 Cardiology Section, West Roxbury, MA, USA4 Leiden University Medical Center, Leiden, NL, The Netherlands
ABSTRACT- Objectives: Studies in our laboratory have shown that mast cells influence the development of radiation-induced heart disease (RIHD). Moreover, evidence suggests that mast cells may regulate the levels and effects of endothelin-1 (ET-1), a peptide that plays an important role in cardiovascular function and cardiac remodeling via its two receptors, ETA and ETB. This study used a mast cell-deficient rat model to investigate possible interactions between mast cells and the cardiac endothelin system in RIHD. Methods: Mast cell-deficient (Ws/Ws) and mast cell-competent (+/+) rats were exposed to 18 Gy localized single dose irradiation of the heart. Histological changes were assessed 1 week, 3 months and 6 months after irradiation. Real-time PCR and immunohistochemistry were used to assess steady-state mRNA levels and localization of ET-1, ETA and ETB. Functional changes were assessed using echocardiography and Langendorff isolated heart preparation. Results: Irradiated hearts from mast cell-competent rats exhibited more severe myocardial degeneration, but less severe diastolic dysfunction than irradiated hearts from mast cell-deficient rats. Post-radiation ET-1 mRNA levels were strikingly increased in mast cell-competent hearts, but not in mast cell-deficient hearts. Cardiac mast cells exhibited prominent ETA and ETB immunoreactivity. Conclusions: These data suggest that crosstalk between mast cells and the endothelin system may be important during the development of RIHD and point to ET-1 and/or its receptors as possible therapeutic targets to reduce RIHD.
Key words: heart, radiation injury, mast cells, endothelin-1
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