NIH Research Festival
Myocarditis is a major cause of heart failure and sudden death in young adults and adolescent. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies are often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis Sativa (Marijuana), which has been reported to exert numerous anti-inflammatory and tissue protective effects in various preclinical disease models, independent from conventional cannabinoid 1 and 2 receptors. CBD-based formulations have been approved for the management of multiple sclerosis in numerous countries, and CBD also received recent FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization against cardiac myosin resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T cell-infiltration, profound inflammatory response, fibrosis (measured by Q-PCR, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ mediated inflammatory response, myocardial fibrosis and cardiac dysfunction (improved both load-dependent and -independent indices of myocardial contractility and attenuated diastolic dysfunction and stiffness) in mice. Thus, CBD may represent a promising new treatment for management of autoimmune myocarditis.
Scientific Focus Area: Molecular Pharmacology
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