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

Biochem Biophys Res Commun. 2026 Oct 9;839:154720. doi: 10.1016/j.bbrc.2026.154720. Online ahead of print.

ABSTRACT

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.

PMID:42858650 | DOI:10.1016/j.bbrc.2026.154720