Abstract
Purpose: Radiation-induced heart disease (RIHD) is a delayed effect of radiotherapy for cancers of the chest, such as breast, esophageal, and lung. Kinins are small peptides with cardioprotective properties. We previously used a rat model that lacks the precursor kininogen to demonstrate that kinins are involved in RIHD. Here, we examined the role of the kinin B2 receptor (B2R) in early radiation-induced signaling in the heart.Materials and methods: Male Brown Norway rats received the B2R-selective antagonist HOE-140 (icatibant) via osmotic minipump from 5 days before until 4 weeks after 21 Gy local heart irradiation. At 4 weeks, signaling events were measured in left ventricular homogenates and nuclear extracts using western blotting and real-time polymerase chain reaction. Numbers of CD68-positive (monocytes/macrophages), CD2-positive (T-lymphocytes), and mast cells were measured using immunohistochemistry.Results: Radiation-induced c-Jun phosphorylation and nuclear translocation were enhanced by HOE-140. HOE-140 did not modify endothelial nitric oxide synthase (eNOS) phosphorylation or alter numbers of CD2-positive or mast cells, but enhanced CD68-positive cell counts in irradiated hearts.Conclusions: B2R signaling may regulate monocyte/macrophage infiltration and c-Jun signals in the irradiated heart. Although eNOS is a main target for kinins, the B2R may not regulate eNOS phosphorylation in response to radiation.
Highlights
Radiation therapy (RT) is a leading treatment option for cancer, with estimates that over 50% of patients receive such treatment (DeSantis et al 2014)
ENOS is a main target for kinins, the B2 receptor (B2R) may not regulate endothelial nitric oxide synthase (eNOS) phosphorylation in response to radiation
RT is useful in decreasing morbidity from such cancers, all or part of the heart can be situated in the field of radiation
Summary
Radiation therapy (RT) is a leading treatment option for cancer, with estimates that over 50% of patients receive such treatment (DeSantis et al 2014). Patients with thoracic cancers such as lung, breast, and Hodgkin’s lymphoma frequently receive radiation therapy either in conjunction with conventional antineoplastics or alone. Adjuvant whole-breast radiation after breast-conserving surgery, for example, has been shown to reduce the risk of local reoccurrences by about two-thirds (Early Breast Cancer Trialists’ Collaborative Group 2011). RT is useful in decreasing morbidity from such cancers, all or part of the heart can be situated in the field of radiation. The resulting pathologies, collectively known as radiation-induced heart disease (RIHD), can lead to the intersection of the two leading causes of morbidity and mortality worldwide: cancer and cardiovascular diseases (Fuster and Voûte 2005)
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