Targeting the Endocannabinod System to Limit Myocardial and Cerebral Ischemic and Reperfusion Injury
Ronald F. Tuma and Sabine Steffens
Pages 46-58 (13)
Coronary and carotid arterial occlusion due to thrombosis after atherosclerotic plaque rupture is the major cause of myocardial and cerebral infarction. Together these acute events represent the leading cause of death worldwide. Early reperfusion is the best method to salvage the ischemic organ; however, it leads to additional damage known as reperfusion injury. A large number of experimental studies has been performed in the past aimed at targeting individual mediators of reperfusion injury such as treatment with anti-oxidants or anti-inflammatory agents. Although many agents proved beneficial in animal models of myocardial or cerebral ischemia/reperfusion, the attempts to translate these protective effects into clinical practice were mostly disappointing. Elucidating the complex cellular and molecular mechanisms involved in ischemic cell death is crucial for the development of more efficient drugs in order to improve current treatment strategies. The aim of this review is to discuss cannabinoid and endocannabinoid-mediated effects in the pathogenesis of myocardial infarction and reperfusion injury, post-myocardial infarction remodeling, as well as ischemic stroke and reperfusion injury. We report experimental evidence suggesting that targeting the endocannabinoid system might evolve as a novel therapeutic concept to limit the devastating consequences of these acute vascular events through a wide variety of mechanisms, including lowering inflammation, oxidative stress, fibrosis, and excitotoxicity, and enhanced blood flow.
Endocannabinoids, cannabinoid receptors, ischemia reperfusion injury, inflammation, remodeling, fibrosis, excitotoxicity, thrombosis, atherosclerotic plaque rupture, ischemic organ, anti-inflammatory agents, cerebral ischemia/reperfusion, cannabinoid and endocannabinoid-mediated effects, reperfusion injury, post-myocardial infarction remodeling
Division of Cardiology, Department of Internal Medicine, University Hospital, Foundation for Medical Researches, Avenue Roseraie 64, 1211 Geneva, Switzerland.