The relationship between the cannabinoids and cardiac remodelling: A comprehensive review of pivotal mechanisms and emerging evidence

Cardiac remodelling and fibrosis after myocardial infarction or during chronic diseases, such as arterial and pulmonary hypertension or diabetes mellitus, continue to be the more important prognostic factors in determining survival, and so the search for effective anti-fibrotic interventions is an important target for research and therapy in cardiology. It has been suggested that compounds with anti-inflammatory and antioxidant properties (such as cannabinoids) may represent interesting therapeutic alternatives, due to their ability to influence pro-fibrotic signalling and inhibit pathological extracellular matrix deposition in the heart. This review describes the more important signalling pathways involved in cardiac fibrosis and some new concepts regarding the utility of cannabinoids and modulation of the endocannabinoid system (ESC) as therapeutic interventions against cardiac fibrosis. The studies presented in this review suggest that specific cannabinoid type 2 receptor activation and peripheral cannabinoid Type 1 receptor blockade appear particularly promising. The potential for the cardioprotective anti-fibrotic effects of cannabinoids and ECS modulators appears to lie in their high antioxidant and anti-inflammatory efficacy, which limits the progression of fibrotic lesions and restores normal regulation of molecular signalling pathways.