Development of a Mouse Cardiac Sarcoidosis Model Using Carbon Nanotubes

Abstract

Sarcoidosis, a granulomatous disorder of unknown etiology affecting multiple organs. It is often a benign disease but can have significant morbidity and mortality when the heart is involved (often presenting with clinical manifestations such as conduction irregularities and heart failure). This study addresses a critical gap in cardiac sarcoidosis (CS) research by developing a robust animal model. The absence of a reliable animal model for cardiac sarcoidosis is a significant obstacle in advancing understanding and treatment of this condition. The proposed model utilizes carbon nanotube injection and transverse aortic constriction as stressors. Intramyocardial injection of carbon nanotubes induces histiocytes typical of sarcoid granulomas in the heart but shows limited effects on fibrosis or cardiac function. Priming the immune system with transverse aortic constriction prior to intramyocardial injection of carbon nanotubes enhances cardiac fibrosis, diminishes cardiac function, and impairs cardiac conduction. This novel, easily executable model may serve as a valuable tool for disease profiling, biomarker identification, and therapeutic exploration.

Keywords: cardiac sarcoidosis; fibrosis; heart; mouse model; sarcoidosis.