Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
Can J Cardiol. 2013 Apr;29(4):499-509. doi: 10.1016/j.cjca.2012.06.003. Epub 2012 Aug 24.
The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease.
Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue.
In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics.
These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.
内源性大麻素系统据称在心血管疾病的发病机制中发挥作用。该系统也在脂肪组织中表达，因此通过调节代谢触发的炎症，可能参与心脏紊乱。本研究旨在确定心脏疾病中外周血心脏脂肪组织中内源性大麻素系统的相关性。
通过 Western blot 分析冠心病患者（缺血性心脏病；N = 18）或瓣膜手术患者（非缺血性心脏病；N = 15）及从心外膜脂肪组织分离的前脂肪细胞中内源性大麻素受体 CB1 和 CB2、内源性大麻素降解酶脂肪酸酰胺水解酶、蛋白激酶 A (PKA)、磷脂酶 C (PLC)、蛋白激酶 C (PKC)、内皮型一氧化氮合酶 (eNOS) 和诱导型 (iNOS)、细胞外信号调节激酶 1 和 2 (ERK1/2)（再灌注损伤挽救激酶途径的一个成员）的表达。
在缺血性心脏病患者中，CB1 与 CB2 的表达比例向 CB1 倾斜，同时 PKA 激活增加。相反，在非缺血性心脏病患者中，CB2、脂肪酸酰胺水解酶、PLC 和 PKC 以及 ERK1/2 上调。此外，缺血性心脏病患者的前脂肪细胞中 NO 产生和 iNOS 与 eNOS 的比值更高。
这些结果表明，与非缺血性心脏病患者相比，内源性大麻素系统在缺血性心脏病患者中有不同的调节和功能。因此，虽然在没有缺血性心脏病的患者中 CB2、PLC 和 PKC、ERK1/2 和 eNOS 表达更强烈，但高 CB1 和 PKA 表达与低生存细胞内途径激活和 iNOS 激活相关在缺血性心脏病患者中。内源性大麻素系统在缺血性心脏病中的变化可能导致心脏功能障碍，因此代表了一个潜在的治疗靶点。
