“Hepatic cardiomyopathy, a special type of heart failure develops in up to 50% of patients with cirrhosis and is a major determinant of survival. However, there is no reliable model of hepatic cardiomyopathy in mice. Herein we aimed to characterize the detailed hemodynamics of mice with bile-duct ligation (BDL)-induced liver fibrosis, by monitoring echocardiography and intracardiac pressure-volume (PV) relationships and myocardial structural alterations. Treatment of mice with a selective cannabinoid-2 receptor (CB2 -R) agonist, known to attenuate inflammation and fibrosis, was used to explore the impact of liver inflammation, fibrosis on cardiac function.
MAIN RESULTS:
BDL induced massive inflammation (increased leukocyte infiltration, inflammatory cytokines and chemokines), oxidative stress, microvascular dysfunction, and fibrosis in the liver. These pathological changes were accompanied by impaired diastolic, systolic and macrovascular functions, cardiac inflammation (increased MIP1, interleukin-1, P-selectin, CD45+ cells) and oxidative stress (increased malondialdehyde, 3-nitrotyrosine and NADPH-oxidases). CB2 -R up-regulation was observed both in livers and hearts of mice exposed to BDL. CB2 -R activation markedly improved hepatic inflammation, impaired microcirculation, fibrosis. CB2 -R activation also decreased serum TNF-alpha levels, and improved cardiac dysfunction, myocardial inflammation and oxidative stress underlining the importance of inflammatory mediators in the pathology of hepatic cardiomyopathy.
CONCLUSION:
We propose BDL-induced cardiomyopathy in mice as a model for hepatic/cirrhotic cardiomyopathy. This cardiomyopathy, similarly to cirrhotic cardiomyopathy in humans, is characterized by systemic hypotension, impaired macro- and microvascular function accompanied by both systolic and diastolic dysfunction. Our results indicate that the liver-heart inflammatory axis has a pivotal pathophysiological role in the development of hepatic cardiomyopathy. Thus, controlling liver and/or myocardial inflammation (e.g. with selective CB2-R agonists) may delay/prevent the development of cardiomyopathy in severe liver disease. ”
https://www.ncbi.nlm.nih.gov/pubmed/31469200
https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.30916
“The Endocannabinoid (eCB) system and its role in many physiological and pathological conditions is well described and accepted, and includes cardiovascular disorders. However, the eCB system has been expanded to an “-ome”; the endocannabinoidome (eCBome) that includes endocannabinoid-related mediators, their protein targets and metabolic enzymes, many of which significantly impact upon cardiometabolic health. These recent discoveries are here summarized with a special focus on their potential involvement in atherosclerosis. We described the role of classical components of the eCB system (eCBs, CB1 and CB2 receptors) and eCB-related lipids, their regulatory enzymes and molecular targets in atherosclerosis. Furthermore, since increasing evidence points to significant cross-talk between the eCBome and the gut microbiome and the gut microbiome and atherosclerosis, we explore the possibility that a gut microbiome – eCBome axis has potential implications in atherosclerosis.”
“The endocannabinoid system (ECS) is an extensive endogenous signaling system with multiple elements, the number of which may be increasing as scientists continue to elucidate its role in human health and disease. The ECS is seemingly ubiquitous in animal species and is modulated by diet, sleep, exercise, stress, and a multitude of other factors, including exposure to phytocannabinoids, like 
