Endocannabinoids and cannabinoid receptors in ischaemia–reperfusion injury and preconditioning

Abstract

Ischaemia-reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB 1 /CB 2 receptordependent and -independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB 1 receptor agonists or knockout mice demonstrated CB 1 receptor-dependent protection against cerebral I/R injury in various animal models. In contrast, several follow-up reports have shown protection afforded by CB 1 receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB 2 receptor agonists and/or knockout mice have provided compelling evidence that CB 2 receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB 2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R-induced tissue damage.

Association of polymorphisms in the endocannabinoid system genes with myocardial infarction and plasma cholesterol levels

“…ECS have been implicated in the protective effects of ischemic preconditioning through cannabinoid receptor dependent and independent mechanisms. However they may also contribute to the cardiovascular collapse associated with myocardial infarction and circulatory shock 19 . Lower FAAH activity due to SNP results in decreased degradation of AEA with subsequent increase in plasma AEA levels which may have negative effects on vasculature and may represent a risk factor of atherosclerosis.…”

Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

“…Neuronal degeneration and death arising from excessive excitatory activity reflect the vulnerability of the brain to excitotoxic insults. In the excitotoxicity field, much attention has been applied to potential strategies to preserve learning and memory and other brain functions, including the neuroprotective abilities of specific signaling lipids that make up the family of endocannabinoids (for more detail see Hwang J, et al [1] Zanettini C, et al [2], Pacher and Hasko [3], and Janero DR, et al [4]). Multiple studies have linked the principal endocannabinoids in the central nervous system, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with protection against numerous diseases, including Alzheimer's, Parkinson's, and Huntington's disease, epileptic seizures, and stroke/ischemic brain damage [5][6][7][8][9][10][11][12][13][14].…”

Possible Activation of the Immune System by Chronic Peripheral Nesfatin-1 Application at the Acute Phase of Ischemia/Reperfusion Injury

“…At present, it is known that ischemia and reperfusion leads to the activation of cell death programs, including apoptosis and necrosis, and that reperfusion injury is characterized by autoimmune responses associated with the activation of innate and adaptive immune responses and inflammatory cell trafficking into the diseased organ (22)(23)(24). Moreover, I/R is the pivotal mechanism of the organ injury during transplantation and is a multifactorial process that affects graft function after transplantation (25,26). The reason is that transplantation is always associated with I/R injury as well as inflammation and rejection (27).…”