Stage-dependent expression of CB1 and CB2 receptors and their vascular effects during the progression of diet-induced atherosclerosis.

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with ischemic heart disease and stroke representing the most common clinical manifestations. Atherosclerosis, a chronic inflammatory disorder of the arterial wall, constitutes the primary pathological basis of these conditions. Recent studies have implicated the endocannabinoid system (ECS), which includes cannabinoid receptors CB1 and CB2, their endogenous ligands, and metabolic enzymes, in the pathophysiology of atherosclerosis. In the present study, we explored the molecular and functional interactions between the ECS and diet-induced atherosclerosis in Wistar rats. Our results show distinct expression patterns of CB1 and CB2 receptors in the aortic wall, with significant downregulation observed in the advanced stages of atherosclerosis. Functional assays demonstrated stage-dependent vascular responses to selective CB1 and CB2 agonists, indicating that modulation of the ECS influences vascular tone and blood pressure. Additionally, biochemical analysis of endocannabinoids and their catabolic enzymes, including 2-arachidonoylglycerol (2-AG)/monoacylglycerol lipase (MAGL) and anandamide (AEA)/fatty acid amide hydrolase (FAAH), revealed dynamic alterations throughout the course of disease progression. These findings underscore the critical role of the ECS in vascular homeostasis and suggest that cannabinoid-based therapeutic strategies may hold potential for the management of atherosclerotic cardiovascular disease.