title: Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury.
abstract: Endocannabinoid system is reported to be activated during myocardial ischemia-reperfusion (IR) injury and protects against heart injury. We, therefore, observed changes in endocannabinoids levels during acute myocardial infarction (AMI) and myocardial IR injury and evaluated the role of cannabinoid-2 (CB2) receptor in infarct and IR heart injury. In contrast to 16 control patients with normal coronary artery angiogram, the endocannabinoid 2-arachidonoylglycerol level in the infarct-side coronary artery of 23 AMI patients increased significantly, with increased reactive oxygen species and tumor necrosis factor-α levels in both infarct-side coronary artery and radial artery. Then, 35 C57BL/6J mice were made into SHAM, AMI, or IR models. AMI and IR groups were treated with CB2-selective agonist HU308 ((+)-(1aH,3H,5aH)-4-[2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbinol), with or without CB2-selective antagonist AM630 [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone through intraperitoneal injection. Compared with the SHAM, expressions of cannabinoid CB1/CB2 receptor proteins in AMI/IR animals were upregulated; production of 2-arachidonoylglycerol and anandamide and release of reactive oxygen species and tumor necrosis factor-α also increased. HU308 significantly decreased the infarct size and the levels of reactive oxygen species and tumor necrosis factor-α in AMI/IR animals. However, these effects were blocked by AM630. In conclusion, the endocannabinoid system was activated during AMI and IR, and CB2 receptor activation produces a protective role, thus offering a novel pharmaceutical target for treating these diseases.
authors: Department of Cardiology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors: Peng-Fei
authors: PF
authors: Wang
authors: Li-Sheng
authors: LS
authors: Jiang
authors: Jun
authors: J
authors: Bu
authors: Xiao-Jin
authors: XJ
authors: Huang
authors: Wei
authors: W
authors: Song
authors: Yong-Ping
authors: YP
authors: Du
authors: Ben
authors: B
authors: He
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology; D016022:Case-Control Studies; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D017534:Radial Artery; D017382:Reactive Oxygen Species / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D007211:Indoles; D017382:Reactive Oxygen Species; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; C094503:glyceryl 2-arachidonate; C402416:HU 308; C094023:iodopravadoline