cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2026-3133cardiotomsk-3133Research ArticleСтатьиРоль каннабиноидных рецепторов CB1 и CB2 при ишемически-реперфузионном повреждении миокарда: кардиопротекторные и вазопротекторные эффекты (обзор литературы)The Role of CB1 and CB2 Cannabinoid Receptors in Myocardial Ischemia-Reperfusion Injury: Cardioprotective and Vasculoprotective Effects (a literature review)https://orcid.org/0000-0002-8543-6027СтепановИ. В.StepanovI. V.

Степанов Иван Вадимович, канд. мед. наук, заведующий патологоанатомическим отделением, врач-патологоанатом

634012, Российская Федерация, Томск, ул. Киевская, 111а

Ivan V. Stepanov, Cand. Sci. (Med.), Head of the Pathological Department

111a, Kievskaya str., Tomsk, 634012, Russian Federation

i_v_stepanov@mail.ruhttps://orcid.org/0000-0002-5890-071XГорбуновА. С.GorbunovA. S.

Горбунов Александр Сергеевич, канд. мед. наук, старший научный сотрудник, лаборатория экспериментальной кардиологии

634012, Российская Федерация, Томск, ул. Киевская, 111а

Alexander S. Gorbunov, Cand. Sci. (Med.), Senior Scientist, Laboratory of Experimental Cardiology

111a, Kievskaya str., Tomsk, 634012, Russian Federation

gas@cardio-tomsk.ruhttps://orcid.org/0000-0002-6020-1598МасловЛ. Н.MaslovL. N.

Маслов Леонид Николаевич, д-р мед. наук, профессор, заведующий лабораторией экспериментальной кардиологии

634012, Российская Федерация, Томск, ул. Киевская, 111а

Leonid N. Maslov, Dr. Sci. (Med.), Professor, Head of Laboratory of Experimental Cardiology

111a, Kievskaya str., Tomsk, 634012, Russian Federation

maslov@cardio-tomsk.ruНаучно-исследовательский институт кардиологии, Томский национальный исследовательский медицинский центр Российской академии наук (НИИ кардиологии Томского НИМЦ)РоссияCardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences (Cardiology Research Institute, Tomsk NRMC)Russian Federation20221008202600Принято в печать3133Copyright © Степанов И.В., Горбунов А.С., Маслов Л.Н., 20222022Степанов И.В., Горбунов А.С., Маслов Л.Н.Stepanov I.V., Gorbunov A.S., Maslov L.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/3133

Ишемически-реперфузионное повреждение сердца остается одной из ключевых причин неблагоприятного течения постинфарктного периода, способствуя увеличению размеров необратимо поврежденного миокарда, развитию микроваскулярной дисфункции, выраженной воспалительной реакции и патологическому ремоделированию сердца. В последние годы особое внимание уделяется изучению эндоканнабиноидной системы как одного из регуляторов клеточной адаптации к ишемии-реперфузии.

Цель обзора: обобщить современные экспериментальные данные о роли каннабиноидных рецепторов CB1 и CB2 в механизмах кардиопротекции и вазопротекции при ишемически-реперфузионном повреждении миокарда. В обзоре рассмотрены сведения о локализации и экспрессии каннабиноидных рецепторов в миокарде и сосудистой стенке, особенностях их внутриклеточных сигнальных путей и функциональном значении при ишемии-реперфузии. Проанализированы результаты экспериментальных исследований, посвященных влиянию активации рецепторов CB1 и CB2 на размер инфаркта миокарда, выраженность воспалительной реакции, эндотелиальную функцию, микроциркуляторные нарушения и процессы постинфарктного ремоделирования. Также проведен анализ экспериментальных данных, подтверждающих участие каннабиноидных рецепторов CB1 и CB2 в реализации кардиопротекторных эффектов ишемического, дистантного ишемического прекондиционирования, посткондиционирования, теплового стресса. Представленные данные свидетельствуют о том, что функциональные эффекты каннабиноидных рецепторов зависят от их подтипа, характера активации и условий экспериментальной модели. Активация рецепторов CB2 в большинстве экспериментальных моделей сопровождается выраженными противовоспалительными, вазопротекторными и кардиопротекторными эффектами, тогда как роль рецепторов CB1 представляется более сложной и определяется особенностями экспериментальной модели ишемически-реперфузионного повреждения, временем и характером активации рецептора. Совокупность имеющихся данных позволяет рассматривать каннабиноидные рецепторы как мишень для перспективной разработки новых фармакологических подходов к профилактике ишемически-реперфузионного повреждения миокарда и неблагоприятного ремоделирования сердца после инфаркта миокарда.

Myocardial ischemia-reperfusion injury remains a major determinant of adverse post-infarction outcomes, contributing to irreversible myocardial damage, coronary microvascular dysfunction, an exaggerated inflammatory response, and pathological cardiac remodeling. In recent years, the endocannabinoid system has emerged as an important regulator of cellular adaptation to ischemia-reperfusion injury.

Aim: To summarize current experimental data on the role of CB1 and CB2 cannabinoid receptors in the mechanisms of cardioprotection and vasculoprotection in myocardial ischemia-reperfusion injury. The review assesses the localization and expression of cannabinoid receptors in the myocardium and vascular wall, their intracellular signaling pathways, and their functional significance in ischemia-reperfusion injury. Experimental studies on the effects of CB1 and CB2 receptor activation on infarct size, inflammatory response, endothelial function, coronary microvascular dysfunction, and post-infarction cardiac remodeling are discussed. Particular attention is also given to experimental data confirming the involvement of CB1 and CB2 receptors in the cardioprotective mechanisms of ischemic preconditioning, remote ischemic preconditioning, postconditioning, and heat stress. The available data indicate that the biological effects of cannabinoid receptors depend on receptor subtype, the mode of receptor activation, and the experimental model employed. In most experimental studies, activation of CB2 receptors has been associated with pronounced anti-inflammatory, vasculoprotective, and cardioprotective effects, whereas the role of CB1 receptors appears to be more complex and is influenced by the characteristics of the experimental model of myocardial ischemia-reperfusion injury, as well as the timing and pattern of receptor activation. Overall, current data suggest that cannabinoid receptors represent promising therapeutic targets for the development of novel pharmacological strategies aimed at preventing myocardial ischemia-reperfusion injury and adverse cardiac remodeling following myocardial infarction.

инфаркт миокардаишемически-реперфузионное повреждениеканнабиноидные рецепторы CB1каннабиноидные рецепторы CB2ремоделирование сердцаmyocardial infarctionmyocardial ischemia-reperfusion injuryCB1 cannabinoid receptorCB2 cannabinoid receptorcardiac remodelingработа выполнена при поддержке Российского научного фонда (грант № 25-25-00595); при поддержке государственного задания Министерства науки и высшего образования РФ 122020300042-4 подготовлены глава «Вазопротективные эффекты агонистов рецепторов CB1 и CB2» и «Заключение».this work was supported by the Russian Science Foundation (grant no. 25-25-00595). The chapter “Vasoprotective Effects of CB1 and CB2 Receptor Agonists” and “Conclusion” were prepared with the support of the state assignment of the Ministry of Science and Higher Education of the Russian Federation 122020300042-4.ReferencesПантелеев О.О., Рябов В.В. Кардиогенный шок: что нового? Сибирский журнал клинической и экспериментальной медицины. 2022;36(4):45–51. DOI: 10.29001/2073-8552-2021-36-4-45-51 EDN: TGEJXOPanteleev O.O., Ryabov V.V. Cardiogenic shock: What's new? Siberian Journal of Clinical and Experimental Medicine. 2022;36(4):45–51. (In Russ). DOI: 10.29001/2073-8552-2021-36-4-45-51 EDN: TGEJXORyabov V.V., Maslov L.N., Vyshlov E.V., et al. Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury. Int. J. Mol. Sci. 2024;25:897. DOI: 10.3390/ijms25020897 EDN: GUHALTRyabov V.V., Maslov L.N., Vyshlov E.V., et al. Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury. Int. J. Mol. Sci. 2024;25:897. DOI: 10.3390/ijms25020897 EDN: GUHALTZavadovsky K.V., Ryabov V.V., Vyshlov E.V., et al. Intra-myocardial hemorrhage and cardiac microvascular injury in ischemia/reperfusion. A systematic review of current evidences. Curr. Probl. Cardiol. 2025;50:102918. DOI: 10.1016/j.cpcardiol.2024.102918 EDN: DQONUYZavadovsky K.V., Ryabov V.V., Vyshlov E.V., et al. Intra-myocardial hemorrhage and cardiac microvascular injury in ischemia/reperfusion. A systematic review of current evidences. Curr. Probl. Cardiol. 2025;50:102918. DOI: 10.1016/j.cpcardiol.2024.102918 EDN: DQONUYАлексеева Ю.В., Вышлов Е.В., Павлюкова Е.Н. и др. Влияние различных типов микрососудистого повреждения на функцию левого желудочка у пациентов с первичным инфарктом миокарда с подъемом сегмента ST. Кардиология. 2021;61(5):23–31. DOI: 10.18087/cardio.2021.5.n1500 EDN: ROQNIWAlekseeva Y.V., Vyshlov E.V., Pavlyukova E.N., et al. Impact of microvascular injury various types on function of left ventricular in patients with primary myocardial infarction with ST segment elevation. Kardiologiia. 2021;61:23–31. (In Russ). DOI: 10.18087/cardio.2021.5.n1500 EDN: ROQNIWMaslov L.N., Khaliulin I., Zhang Y., et al. Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists. J. Cardiovasc. Pharmacol. Ther. 2016;21:262–272. DOI: 10.1177/1074248415612593 EDN: WTAJCHMaslov L.N., Khaliulin I., Zhang Y., et al. Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists. J. Cardiovasc. Pharmacol. Ther. 2016;21:262–272. DOI: 10.1177/1074248415612593 EDN: WTAJCHMatsuda L.A., Lolait S.J., Brownstein M.J., et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561–564. DOI: 10.1038/346561a0Matsuda L.A., Lolait S.J., Brownstein M.J., et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561–564. DOI: 10.1038/346561a0Munro S., Thomas K.L., Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365:61–65. DOI: 10.1038/365061a0Munro S., Thomas K.L., Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365:61–65. DOI: 10.1038/365061a0Galiègue S., Mary S., Marchand J., et al. Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations. Eur. J. Biochem. 1995;232:54–61. DOI: 10.1111/j.1432-1033.1995.tb20780.xGaliègue S., Mary S., Marchand J., et al. Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations. Eur. J. Biochem. 1995;232:54–61. DOI: 10.1111/j.1432-1033.1995.tb20780.xDevane W.A., Hanuš L., Breuer A., et al. Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor. Science. 1992;258:1946–1949. DOI: 10.1126/science.1470919Devane W.A., Hanuš L., Breuer A., et al. Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor. Science. 1992;258:1946–1949. DOI: 10.1126/science.1470919Mechoulam R., Ben-Shabat S., Hanus L., et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 1995;50:83–90. DOI: 10.1016/0006-2952(95)00109-DMechoulam R., Ben-Shabat S., Hanus L., et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 1995;50:83–90. DOI: 10.1016/0006-2952(95)00109-DShmist Y.A., Goncharov I., Eichler M., et al. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Mol. Cell. Biochem. 2006;283:75-83. DOI: 10.1007/s11010-006-2346-y EDN: MCSICHShmist Y.A., Goncharov I., Eichler M., et al. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Mol. Cell. Biochem. 2006;283:75-83. DOI: 10.1007/s11010-006-2346-y EDN: MCSICHQian L., Zhang S., Lin C., et al. Depression exacerbates myocardial ischemia-reperfusion injury in mice via CNR2 gene and MIF-AMPK signaling pathway. Int. J. Cardiol. 2024;416:132505. DOI: 10.1016/j.ijcard.2024.132505Qian L., Zhang S., Lin C., et al. Depression exacerbates myocardial ischemia-reperfusion injury in mice via CNR2 gene and MIF-AMPK signaling pathway. Int. J. Cardiol. 2024;416:132505. DOI: 10.1016/j.ijcard.2024.132505Duerr G.D., Heinemann J.C., Kley J., et al. Myocardial maladaptation to pressure overload in CB2 receptor-deficient mice. J. Mol. Cell. Cardiol. 2019;133:86–98. DOI: 10.1016/j.yjmcc.2019.06.003Duerr G.D., Heinemann J.C., Kley J., et al. Myocardial maladaptation to pressure overload in CB2 receptor-deficient mice. J. Mol. Cell. Cardiol. 2019;133:86–98. DOI: 10.1016/j.yjmcc.2019.06.003Möhnle P., Schütz S.V., Schmidt M., et al. MicroRNA-665 is involved in the regulation of the expression of the cardioprotective cannabinoid receptor CB2 in patients with severe heart failure. Biochem. Biophys. Res. Commun. 2014;451:516–521. DOI: 10.1016/j.bbrc.2014.08.008Möhnle P., Schütz S.V., Schmidt M., et al. MicroRNA-665 is involved in the regulation of the expression of the cardioprotective cannabinoid receptor CB2 in patients with severe heart failure. Biochem. Biophys. Res. Commun. 2014;451:516–521. DOI: 10.1016/j.bbrc.2014.08.008Piotrowska Ż., Niezgoda M., Łebkowski W., et al. Sex differences in distribution of cannabinoid receptors (CB1 and CB2), S100A6 and CacyBP/SIP in human ageing hearts. Biol. Sex Differ. 2018;9:50. DOI: 10.1186/s13293-018-0209-3Piotrowska Ż., Niezgoda M., Łebkowski W., et al. Sex differences in distribution of cannabinoid receptors (CB1 and CB2), S100A6 and CacyBP/SIP in human ageing hearts. Biol. Sex Differ. 2018;9:50. DOI: 10.1186/s13293-018-0209-3Schloss M.J., Horckmans M., Guillamat-Prats R., et al. 2-Arachidonoylglycerol mobilizes myeloid cells and worsens heart function after acute myocardial infarction. Cardiovasc. Res. 2019;115:602–613. DOI: 10.1093/cvr/cvy242Schloss M.J., Horckmans M., Guillamat-Prats R., et al. 2-Arachidonoylglycerol mobilizes myeloid cells and worsens heart function after acute myocardial infarction. Cardiovasc. Res. 2019;115:602–613. DOI: 10.1093/cvr/cvy242Wagner J.A., Abesser M., Harvey-White J., Ertl G. 2-Arachidonylglycerol Acting on CB1 Cannabinoid Receptors Mediates Delayed Cardioprotection Induced by Nitric Oxide in Rat Isolated Hearts. J. Cardiovasc. Pharmacol. 2006;47:650–655. DOI: 10.1097/01.fjc.0000211752.08949.ebWagner J.A., Abesser M., Harvey-White J., Ertl G. 2-Arachidonylglycerol Acting on CB1 Cannabinoid Receptors Mediates Delayed Cardioprotection Induced by Nitric Oxide in Rat Isolated Hearts. J. Cardiovasc. Pharmacol. 2006;47:650–655. DOI: 10.1097/01.fjc.0000211752.08949.ebDuerr G.D., Heinemann J.C., Dunkel S., et al. Myocardial hypertrophy is associated with inflammation and activation of endocannabinoid system in patients with aortic valve stenosis. Life Sci. 2013;92:976–983. DOI: 10.1016/j.lfs.2013.03.014Duerr G.D., Heinemann J.C., Dunkel S., et al. Myocardial hypertrophy is associated with inflammation and activation of endocannabinoid system in patients with aortic valve stenosis. Life Sci. 2013;92:976–983. DOI: 10.1016/j.lfs.2013.03.014Wang P.-F., Jiang L.-S., Bu J., et al. Cannabinoid-2 Receptor Activation Protects Against Infarct and Ischemia-Reperfusion Heart Injury. J. Cardiovasc. Pharmacol. 2012;59:301–307. DOI: 10.1097/FJC.0b013e3182418997Wang P.-F., Jiang L.-S., Bu J., et al. Cannabinoid-2 Receptor Activation Protects Against Infarct and Ischemia-Reperfusion Heart Injury. J. Cardiovasc. Pharmacol. 2012;59:301–307. DOI: 10.1097/FJC.0b013e3182418997Liu X., Zhang D., Dong X., et al. Pharmacological activation of CB2 receptor protects against ethanol-induced myocardial injury related to RIP1/RIP3/MLKL-mediated necroptosis. Mol. Cell. Biochem. 2020;474:1–14. DOI: 10.1007/s11010-020-03828-1Liu X., Zhang D., Dong X., et al. Pharmacological activation of CB2 receptor protects against ethanol-induced myocardial injury related to RIP1/RIP3/MLKL-mediated necroptosis. Mol. Cell. Biochem. 2020;474:1–14. DOI: 10.1007/s11010-020-03828-1Sun H.-J., Lu Y., Wang H.-W., et al. Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats. Oxid. Med. Cell. Longev. 2017;2017:2186383. DOI: 10.1155/2017/2186383Sun H.-J., Lu Y., Wang H.-W., et al. Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats. Oxid. Med. Cell. Longev. 2017;2017:2186383. DOI: 10.1155/2017/2186383Sugiura T., Kodaka T., Nakane S., et al. Detection of an Endogenous Cannabimimetic Molecule, 2-Arachidonoylglycerol, and Cannabinoid CB1 Receptor mRNA in Human Vascular Cells: Is 2-Arachidonoylglycerol a Possible Vasomodulator? Biochem. Biophys. Res. Commun. 1998;243:838–843. DOI: 10.1006/bbrc.1998.8187Sugiura T., Kodaka T., Nakane S., et al. Detection of an Endogenous Cannabimimetic Molecule, 2-Arachidonoylglycerol, and Cannabinoid CB1 Receptor mRNA in Human Vascular Cells: Is 2-Arachidonoylglycerol a Possible Vasomodulator? Biochem. Biophys. Res. Commun. 1998;243:838–843. DOI: 10.1006/bbrc.1998.8187Lépicier P., Lagneux C., Sirois M.G., Lamontagne D. Endothelial CB1-receptors limit infarct size through NO formation in rat isolated hearts. Life Sci. 2007;81:1373–1380. DOI: 10.1016/j.lfs.2007.08.042Lépicier P., Lagneux C., Sirois M.G., Lamontagne D. Endothelial CB1-receptors limit infarct size through NO formation in rat isolated hearts. Life Sci. 2007;81:1373–1380. DOI: 10.1016/j.lfs.2007.08.042Stanley C.P., Hind W.H., Tufarelli C., O'Sullivan S.E. The endocannabinoid anandamide causes endothelium-dependent vasorelaxation in human mesenteric arteries. Pharmacol. Res. 2016;113:356–363. DOI: 10.1016/j.phrs.2016.08.028Stanley C.P., Hind W.H., Tufarelli C., O'Sullivan S.E. The endocannabinoid anandamide causes endothelium-dependent vasorelaxation in human mesenteric arteries. Pharmacol. Res. 2016;113:356–363. DOI: 10.1016/j.phrs.2016.08.028Ugdyzhekova D.S., Krylatov A.V., Bernatskaya N.A., et al. Activation of Cannabinoid Receptors Decreases the Area of Ischemic Myocardial Necrosis. Bull. Exp. Biol. Med. 2002;133:125–126. DOI: 10.1023/A:1015526217332Ugdyzhekova D.S., Krylatov A.V., Bernatskaya N.A., et al. Activation of Cannabinoid Receptors Decreases the Area of Ischemic Myocardial Necrosis. Bull. Exp. Biol. Med. 2002;133:125–126. DOI: 10.1023/A:1015526217332Lépicier P., Bouchard J., Lagneux C., Lamontagne D. Endocannabinoids protect the rat isolated heart against ischaemia. Br. J. Pharmacol. 2003;139:805–815. DOI: 10.1038/sj.bjp.0705313Lépicier P., Bouchard J., Lagneux C., Lamontagne D. Endocannabinoids protect the rat isolated heart against ischaemia. Br. J. Pharmacol. 2003;139:805–815. DOI: 10.1038/sj.bjp.0705313Underdown N.J., Hiley C.R., Ford W.R. Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechanism. Br. J. Pharmacol. 2005;146:809–816. DOI: 10.1038/sj.bjp.0706391Underdown N.J., Hiley C.R., Ford W.R. Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechanism. Br. J. Pharmacol. 2005;146:809–816. DOI: 10.1038/sj.bjp.0706391Lasukova O.V., Maslov L.N., Ermakov S.Y., et al. Role of cannabinoid receptors in regulation of cardiac tolerance to ischemia and reperfusion. Biol. Bull. 2008;35:404–410. DOI: 10.1134/S1062359008040134Lasukova O.V., Maslov L.N., Ermakov S.Y., et al. Role of cannabinoid receptors in regulation of cardiac tolerance to ischemia and reperfusion. Biol. Bull. 2008;35:404–410. DOI: 10.1134/S1062359008040134Di Filippo C., Rossi F., Rossi S., D'Amico M. Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN. J. Leukoc. Biol. 2004;75:453–459. DOI: 10.1189/jlb.0703303Di Filippo C., Rossi F., Rossi S., D'Amico M. Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN. J. Leukoc. Biol. 2004;75:453–459. DOI: 10.1189/jlb.0703303Montecucco F., Lenglet S., Braunersreuther V., et al. CB2 cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion. J. Mol. Cell. Cardiol. 2009;46:612–620. DOI: 10.1016/j.yjmcc.2008.12.014Montecucco F., Lenglet S., Braunersreuther V., et al. CB2 cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion. J. Mol. Cell. Cardiol. 2009;46:612–620. DOI: 10.1016/j.yjmcc.2008.12.014Defer N., Wan J., Souktani R., et al. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy. FASEB J. 2009;23:2120–2130. DOI: 10.1096/fj.09-129478Defer N., Wan J., Souktani R., et al. The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy. FASEB J. 2009;23:2120–2130. DOI: 10.1096/fj.09-129478Li Q., Shi M., Li B. Anandamide enhances expression of heat shock protein 72 to protect against ischemia-reperfusion injury in rat heart. J. Physiol. Sci. 2013;63:47–53. DOI: 10.1007/s12576-012-0228-5Li Q., Shi M., Li B. Anandamide enhances expression of heat shock protein 72 to protect against ischemia-reperfusion injury in rat heart. J. Physiol. Sci. 2013;63:47–53. DOI: 10.1007/s12576-012-0228-5Waldman M., Hochhauser E., Fishbein M. An ultra-low dose of tetrahydrocannabinol provides cardioprotection. Biochem. Pharmacol. 2013;85:1626–1633. DOI: 10.1016/j.bcp.2013.03.014Waldman M., Hochhauser E., Fishbein M. An ultra-low dose of tetrahydrocannabinol provides cardioprotection. Biochem. Pharmacol. 2013;85:1626–1633. DOI: 10.1016/j.bcp.2013.03.014Li Q., Wang F., Zhang Y.-M., et al. Activation of Cannabinoid Type 2 Receptor by JWH133 Protects Heart Against Ischemia/Reperfusion-Induced Apoptosis. Cell. Physiol. Biochem. 2013;31:693–702. DOI: 10.1159/000350088Li Q., Wang F., Zhang Y.-M., et al. Activation of Cannabinoid Type 2 Receptor by JWH133 Protects Heart Against Ischemia/Reperfusion-Induced Apoptosis. Cell. Physiol. Biochem. 2013;31:693–702. DOI: 10.1159/000350088Li Q., Guo H., Maslov L.N., et al. Mitochondrial permeability transition pore plays a role in the cardioprotection of CB2 receptor against ischemia-reperfusion injury. Can. J. Physiol. Pharmacol. 2014;92:205–214. DOI: 10.1139/cjpp-2013-0293Li Q., Guo H., Maslov L.N., et al. Mitochondrial permeability transition pore plays a role in the cardioprotection of CB2 receptor against ischemia-reperfusion injury. Can. J. Physiol. Pharmacol. 2014;92:205–214. DOI: 10.1139/cjpp-2013-0293Gorbunov A.S., Maslov L.N., Tsibulnikov S.Y., et al. CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated Heart. Bull. Exp. Biol. Med. 2016;162:27-29. DOI: 10.1007/s10517-016-3536-6Gorbunov A.S., Maslov L.N., Tsibulnikov S.Y., et al. CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated Heart. Bull. Exp. Biol. Med. 2016;162:27-29. DOI: 10.1007/s10517-016-3536-6Banaszkiewicz M., Tarwacka P., Krzywonos-Zawadzka A., et al. Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment. Front. Biosci. (Landmark Ed). 2022;27(4):114. DOI: 10.31083/j.fbl2704114Banaszkiewicz M., Tarwacka P., Krzywonos-Zawadzka A., et al. Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment. Front. Biosci. (Landmark Ed). 2022;27(4):114. DOI: 10.31083/j.fbl2704114Zhang M., Tian Q., Liu J. Cannabinoid Receptor-2 agonist AM1241 Attenuates Myocardial Ischemia-Reperfusion-Induced Oxidative Stress in Rats via Nrf2/HO-1 Pathway. Med. Princ. Pract. 2024;1–10. DOI: 10.1159/000540751Zhang M., Tian Q., Liu J. Cannabinoid Receptor-2 agonist AM1241 Attenuates Myocardial Ischemia-Reperfusion-Induced Oxidative Stress in Rats via Nrf2/HO-1 Pathway. Med. Princ. Pract. 2024;1–10. DOI: 10.1159/000540751Wagner J.A., Hu K., Karcher J., et al. CB 1 cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction. Br. J. Pharmacol. 2003;138:1251–1258. DOI: 10.1038/sj.bjp.0705156Wagner J.A., Hu K., Karcher J., et al. CB 1 cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction. Br. J. Pharmacol. 2003;138:1251–1258. DOI: 10.1038/sj.bjp.0705156Wang Y., Ma S., Wang Q., et al. Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci. China Life Sci. 2014;57:201–208. DOI: 10.1007/s11427-013-4604-zWang Y., Ma S., Wang Q., et al. Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci. China Life Sci. 2014;57:201–208. DOI: 10.1007/s11427-013-4604-zLu Y., Akinwumi B.C., Shao Z., Anderson H.D. Ligand Activation of Cannabinoid Receptors Attenuates Hypertrophy of Neonatal Rat Cardiomyocytes. J. Cardiovasc. Pharmacol. 2014;64:420–430. DOI: 10.1097/FJC.0000000000000134Lu Y., Akinwumi B.C., Shao Z., Anderson H.D. Ligand Activation of Cannabinoid Receptors Attenuates Hypertrophy of Neonatal Rat Cardiomyocytes. J. Cardiovasc. Pharmacol. 2014;64:420–430. DOI: 10.1097/FJC.0000000000000134Duerr G.D., Heinemann J.C., Gestrich C., et al. Impaired border zone formation and adverse remodeling after reperfused myocardial infarction in cannabinoid CB2 receptor deficient mice. Life Sci. 2015;138:8–17. DOI: 10.1016/j.lfs.2014.11.005Duerr G.D., Heinemann J.C., Gestrich C., et al. Impaired border zone formation and adverse remodeling after reperfused myocardial infarction in cannabinoid CB2 receptor deficient mice. Life Sci. 2015;138:8–17. DOI: 10.1016/j.lfs.2014.11.005Li X., Han D., Tian Z., et al. Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial Fibrosis via Nrf2-Mediated Inhibition of TGF-β1/Smad3 Pathway in Myocardial Infarction Mice. Cell. Physiol. Biochem. 2016;39:1521–1536. DOI: 10.1159/000447855Li X., Han D., Tian Z., et al. Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial Fibrosis via Nrf2-Mediated Inhibition of TGF-β1/Smad3 Pathway in Myocardial Infarction Mice. Cell. Physiol. Biochem. 2016;39:1521–1536. DOI: 10.1159/000447855Wagner J.A., Hu K., Bauersachs J., et al. Endogenous cannabinoids mediate hypotension after experimental myocardial infarction. J. Am. Coll. Cardiol. 2001;38:2048–2054. DOI: 10.1016/S0735-1097(01)01671-0Wagner J.A., Hu K., Bauersachs J., et al. Endogenous cannabinoids mediate hypotension after experimental myocardial infarction. J. Am. Coll. Cardiol. 2001;38:2048–2054. DOI: 10.1016/S0735-1097(01)01671-0Rudź R., Schlicker E., Baranowska U., et al. Acute Myocardial Infarction Inhibits the Neurogenic Tachycardic and Vasopressor Response in Rats via Presynaptic Cannabinoid Type 1 Receptor. J. Pharmacol. Exp. Ther. 2012;343:198–205. DOI: 10.1124/jpet.112.196816Rudź R., Schlicker E., Baranowska U., et al. Acute Myocardial Infarction Inhibits the Neurogenic Tachycardic and Vasopressor Response in Rats via Presynaptic Cannabinoid Type 1 Receptor. J. Pharmacol. Exp. Ther. 2012;343:198–205. DOI: 10.1124/jpet.112.196816Andrag E., Curtis M.J. Feasibility of targeting ischaemia-related ventricular arrhythmias by mimicry of endogenous protection by endocannabinoids. Br. J. Pharmacol. 2013;169:1840–1848. DOI: 10.1111/bph.12252Andrag E., Curtis M.J. Feasibility of targeting ischaemia-related ventricular arrhythmias by mimicry of endogenous protection by endocannabinoids. Br. J. Pharmacol. 2013;169:1840–1848. DOI: 10.1111/bph.12252Joyeux M. Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts. Cardiovasc. Res. 2002;55:619–625. DOI: 10.1016/S0008-6363(02)00268-7Joyeux M. Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts. Cardiovasc. Res. 2002;55:619–625. DOI: 10.1016/S0008-6363(02)00268-7Hajrasouliha A.R., Tavakoli S., Ghasemi M., et al. Endogenous cannabinoids contribute to remote ischemic preconditioning via cannabinoid CB2 receptors in the rat heart. Eur. J. Pharmacol. 2008;579:246–252. DOI: 10.1016/j.ejphar.2007.09.034Hajrasouliha A.R., Tavakoli S., Ghasemi M., et al. Endogenous cannabinoids contribute to remote ischemic preconditioning via cannabinoid CB2 receptors in the rat heart. Eur. J. Pharmacol. 2008;579:246–252. DOI: 10.1016/j.ejphar.2007.09.034Bouchard J.-F., Lépicier P., Lamontagne D. Contribution of endocannabinoids in the endothelial protection afforded by ischemic preconditioning in the isolated rat heart. Life Sci. 2003;72:1859–1870. DOI: 10.1016/S0024-3205(02)02474-8Bouchard J.-F., Lépicier P., Lamontagne D. Contribution of endocannabinoids in the endothelial protection afforded by ischemic preconditioning in the isolated rat heart. Life Sci. 2003;72:1859–1870. DOI: 10.1016/S0024-3205(02)02474-8González C., Herradón E., Abalo R., et al. Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia-reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS. Diabetes. Metab. Res. Rev. 2011;27:331–340. DOI: 10.1002/dmrr.1176González C., Herradón E., Abalo R., et al. Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia-reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS. Diabetes. Metab. Res. Rev. 2011;27:331–340. DOI: 10.1002/dmrr.1176

The authors declare that there are no conflicts of interest present.