CB2 Cannabinoid Receptor as a Potential Target in Myocardial Infarction: Exploration of Molecular Pathogenesis and Therapeutic Strategies

被引:5
作者
More, Sagar A. [1 ]
Deore, Rucha S. [1 ]
Pawar, Harshal D. [1 ]
Sharma, Charu [2 ]
Nakhate, Kartik T. [1 ]
Rathod, Sumit S. [1 ]
Ojha, Shreesh [3 ]
Goyal, Sameer N. [1 ]
机构
[1] Shri Vile Parle Kelavani Mandals Inst Pharm, Dept Pharmacol, Dhule 424001, Maharashtra, India
[2] United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Internal Med, POB 15551, Al Ain 15551, U Arab Emirates
[3] United Arab Emirates Univ, Coll Med & Hlth Sci, Dept Pharmacol & Therapeut, POB 15551, Al Ain, U Arab Emirates
关键词
CB2; receptors; myocardial infarction; ROS; cytokines; cardiac markers; PROLIFERATOR-ACTIVATED RECEPTOR; PERMEABILITY TRANSITION PORE; ATTENUATES CARDIAC FIBROSIS; NF-KAPPA-B; NITRIC-OXIDE; OXIDATIVE STRESS; ISCHEMIA/REPERFUSION INJURY; ENDOCANNABINOID SYSTEM; INFLAMMATORY RESPONSE; ENDOTHELIAL DYSFUNCTION;
D O I
10.3390/ijms25031683
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The lipid endocannabinoid system has recently emerged as a novel therapeutic target for several inflammatory and tissue-damaging diseases, including those affecting the cardiovascular system. The primary targets of cannabinoids are cannabinoid type 1 (CB1) and 2 (CB2) receptors. The CB2 receptor is expressed in the cardiomyocytes. While the pathological changes in the myocardium upregulate the CB2 receptor, genetic deletion of the receptor aggravates the changes. The CB2 receptor plays a crucial role in attenuating the advancement of myocardial infarction (MI)-associated pathological changes in the myocardium. Activation of CB2 receptors exerts cardioprotection in MI via numerous molecular pathways. For instance, delta-9-tetrahydrocannabinol attenuated the progression of MI via modulation of the CB2 receptor-dependent anti-inflammatory mechanisms, including suppression of pro-inflammatory cytokines like IL-6, TNF-alpha, and IL-1 beta. Through similar mechanisms, natural and synthetic CB2 receptor ligands repair myocardial tissue damage. This review aims to offer an in-depth discussion on the ameliorative potential of CB2 receptors in myocardial injuries induced by a variety of pathogenic mechanisms. Further, the modulation of autophagy, TGF-beta/Smad3 signaling, MPTP opening, and ROS production are discussed. The molecular correlation of CB2 receptors with cardiac injury markers, such as troponin I, LDH1, and CK-MB, is explored. Special attention has been paid to novel insights into the potential therapeutic implications of CB2 receptor activation in MI.
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页数:20
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