Abstract 14880: Interleukin-18 in Radiation-induced Cardiomyopathy
Introduction: Thoracic radiation (XRT) used in treatment of cancer leads to the development of cardiomyopathy, characterized by increased myocardial and pericardial fibrosis. A close link between XRT injury, fibrosis and inflammation exists. Interleukin-18, a proinflammatory cytokines of the IL-1 family, has been shown to promote cardiac fibrosis.
Hypothesis: IL-18 mediates myocardial and pericardial fibrosis following thoracic XRT.
Methods: We exposed C57BL/6J female mice (N=6-12/group) to XRT 20 Gray (Gy). Echocardiography was performed to assess left ventricular (LV) ejection fraction (EF) at baseline, and 3 days and 4 months following XRT. LV catheterization was used to measure the LV end diastolic pressure (EDP), LV peak systolic pressure, +dP/dt and -dP/dt. Masson’s Trichrome was used to quantify interstitial fibrosis and pericardial thickening. Western Blot (WB) and Immunofluorescence (IF) were used to measure IL-18 levels in the heart after XRT. Sham-XRT mice were used as controls.
Results: Thoracic XRT induced a restrictive cardiomyopathy in the mouse characterized by no increase in LV cavity or mass (all P=NS), a mild reduction in resting LVEF (58.5±1.8% vs 65.6±2.2% sham, P <0.05, figure), and significant increase in LVEDP 4 months after XRT (>2-fold increase, P<0.05, Figure). Interstitial fibrosis and pericardial thickening were markedly increased after XRT, and WB and IF analysis showed a significant increase in IL-18 expression at 3 days and 4 months after XRT, with a distribution corresponding with myocardial interstitial and pericardial fibrosis (Figure).
Conclusions: Thoracic XRT causes a restrictive cardiomyopathy characterized by increased IL-18 expression at the site of myocardial interstitial and pericardial fibrosis.
Author Disclosures: E. Mezzaroma: None. R.B. Mikkelsen: None. S. Toldo: None. K. Sharma: None. C. Sonnino: None. A.G. Mauro: None. C. Marchetti: None. A. Alam: None. B.W. Van Tassell: None. D.A. Gewirtz: None. A. Abbate: Research Grant; Modest; Grifols. Other Research Support; Modest; Swedish Orphan Biovitrum. Research Grant; Significant; Novartis.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.