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Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury.
J Cardiovasc Pharmacol 2012; 59(4):301-7JC

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+Show Affiliations

Department of Cardiology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22113346

Citation

Wang, Peng-Fei, et al. "Cannabinoid-2 Receptor Activation Protects Against Infarct and Ischemia-reperfusion Heart Injury." Journal of Cardiovascular Pharmacology, vol. 59, no. 4, 2012, pp. 301-7.
Wang PF, Jiang LS, Bu J, et al. Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury. J Cardiovasc Pharmacol. 2012;59(4):301-7.
Wang, P. F., Jiang, L. S., Bu, J., Huang, X. J., Song, W., Du, Y. P., & He, B. (2012). Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury. Journal of Cardiovascular Pharmacology, 59(4), pp. 301-7. doi:10.1097/FJC.0b013e3182418997.
Wang PF, et al. Cannabinoid-2 Receptor Activation Protects Against Infarct and Ischemia-reperfusion Heart Injury. J Cardiovasc Pharmacol. 2012;59(4):301-7. PubMed PMID: 22113346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury. AU - Wang,Peng-Fei, AU - Jiang,Li-Sheng, AU - Bu,Jun, AU - Huang,Xiao-Jin, AU - Song,Wei, AU - Du,Yong-Ping, AU - He,Ben, PY - 2011/11/25/entrez PY - 2011/11/25/pubmed PY - 2012/8/11/medline SP - 301 EP - 7 JF - Journal of cardiovascular pharmacology JO - J. Cardiovasc. Pharmacol. VL - 59 IS - 4 N2 - 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. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/22113346/Cannabinoid_2_receptor_activation_protects_against_infarct_and_ischemia_reperfusion_heart_injury_ L2 - http://Insights.ovid.com/pubmed?pmid=22113346 DB - PRIME DP - Unbound Medicine ER -