Xu Dengyue, Xu Chennian, Xue Xiaodong, Xu Yinli, Zhao Jikai, Huang Tao, Wang Zhishang, Zhao Qiusheng, Zhou Zijun, Huang Yuting, Yu Liming, Wang Huishan
Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
Postgraduate College, China Medical University, Shenyang, Liaoning, China.
Front Cardiovasc Med. 2022 Oct 14;9:968014. doi: 10.3389/fcvm.2022.968014. eCollection 2022.
Atrial fibrillation (AF) is the most frequent arrythmia managed in clinical practice. Several mechanisms have been proposed to contribute to the occurrence and persistence of AF, in which oxidative stress plays a non-negligible role. The endocannabinoid system (ECS) is involved in a variety physiological and pathological processes. Cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R) are expressed in the heart, and studies have shown that activating CB2R has a protective effect on the myocardium. However, the role of CB2R in AF is unknown.
Angiotensin II (Ang II)-infused mice were treated with the CB2R agonist AM1241 intraperitoneally for 21 days. Atrial structural remodeling, AF inducibility, electrical transmission, oxidative stress and fibrosis were measured in mice.
The susceptibility to AF and the level of oxidative stress were increased significantly in Ang II-infused mice. In addition, nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), NOX4, and oxidized Ca/calmodulin-dependent protein kinase II (ox-CaMKII) were highly expressed. More importantly, treatment with AM1241 activated CB2R, resulting in a protective effect.
The present study demonstrates that pharmacological activation of CB2R exerts a protective effect against AF a potential NOX/CaMKII mechanism. CB2R is a potential therapeutic target for AF.
心房颤动（AF）是临床实践中最常见的心律失常。已提出多种机制促成AF的发生和持续，其中氧化应激起不可忽视的作用。内源性大麻素系统（ECS）参与多种生理和病理过程。大麻素受体1（CB1R）和大麻素受体2（CB2R）在心脏中表达，研究表明激活CB2R对心肌有保护作用。然而，CB2R在AF中的作用尚不清楚。
用血管紧张素II（Ang II）灌注小鼠，并腹腔注射CB2R激动剂AM1241，持续21天。检测小鼠的心房结构重塑、AF诱导性、电传导、氧化应激和纤维化情况。
Ang II灌注小鼠的AF易感性和氧化应激水平显著增加。此外，烟酰胺腺嘌呤二核苷酸磷酸氧化酶2（NOX2）、NOX4和氧化型钙/钙调蛋白依赖性蛋白激酶II（ox-CaMKII）高表达。更重要的是，AM1241治疗激活CB2R，产生保护作用。
本研究表明，CB2R的药理学激活对AF具有保护作用——一种潜在的NOX/CaMKII机制。CB2R是AF的潜在治疗靶点。
