Abstract
Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration 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 with cardiac myosin emmulsified in adjuvant 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 and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell-mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation.
Highlights
The report of the 1995 World HealthOrganization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies [1] defined myocarditis as an inflammatory heart disease associated with cardiac dysfunction
Animals were divided into four experimental groups, namely control (CTL), CFA treated (CFA treated with vehicle; n = 10), experimental autoimmune myocarditis (EAM treated with vehicle; n = 16) and CBD-treated EAM (EAM + CBD; n = 12)
We found significant downregulation of sarco/endoplasmic reticulum ATPase2a2 (SERCA) (Figure 4A), which was reverted by the application of CBD (Figure 4A). 3-NT and 4-HNE content of the left ventricular (LV) was significantly increased in the LV of EAM animals (Figures 4B, C), which was markedly reduced by CBD treatment (Figures 4B, C)
Summary
The report of the 1995 World Health. Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies [1] defined myocarditis as an inflammatory heart disease associated with cardiac dysfunction. Myocarditis is associated with several serious cardiac complications, ranging from sudden cardiac death [2] to chronic heart failure. Myocarditis often results in the development of dilated cardiomyopathy, which is one of the most important indications for cardiac transplantation [3,4]. Different etiologies can lead to the development of myocarditis in humans, such as infectious diseases, autoimmune d iseases, hypersensitivity or toxic reactions to drugs [3]. The course of myocarditis can be separated into acute, subacute and chronic phases [5].
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