PDF(Pubmed)
Abstract：
UNASSIGNED: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5\'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear.
UNASSIGNED: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured.
UNASSIGNED: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A.
UNASSIGNED: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.
UNASSIGNED: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured.
UNASSIGNED: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A.
UNASSIGNED: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.
摘要：
■肝硬化引起的心肌炎症和细胞凋亡是肝硬化心肌病的主要机制之一。CD73，一种常见的细胞外核苷酸酶，也称为5'-核苷酸酶，与多个器官的炎症和免疫进展有关。然而,CD73参与肝硬化心肌炎症和细胞凋亡的机制尚不清楚.
■在这项研究中，通过胆管结扎建立肝硬化心肌病小鼠模型。通过尾静脉注射AAV9（腺相关病毒）-cTNT-NT5E-mCherry，使用超声心动图评估小鼠的心脏功能。通过病理观察和ELISA测定评估心肌炎症浸润和凋亡。CD73、A2AR的表达,凋亡标志物，并测定心肌组织中与NF-κB通路相关的蛋白。
■在肝硬化心肌病小鼠模型的心肌组织中，CD73和A2AR的表达增加。通过AAV9注射和CGS21680刺激A2AR在心肌中的过表达CD73抑制了肝硬化引起的心肌炎症和心肌细胞凋亡。此外,CD73的过表达通过上调腺苷受体A2A的表达来抑制NF-κB途径的激活。
■我们的研究表明，CD73/A2AR信号轴通过NF-κB通路的负反馈调节减轻肝硬化诱导的心肌炎症和凋亡。
■在这项研究中，通过胆管结扎建立肝硬化心肌病小鼠模型。通过尾静脉注射AAV9（腺相关病毒）-cTNT-NT5E-mCherry，使用超声心动图评估小鼠的心脏功能。通过病理观察和ELISA测定评估心肌炎症浸润和凋亡。CD73、A2AR的表达,凋亡标志物，并测定心肌组织中与NF-κB通路相关的蛋白。
■在肝硬化心肌病小鼠模型的心肌组织中，CD73和A2AR的表达增加。通过AAV9注射和CGS21680刺激A2AR在心肌中的过表达CD73抑制了肝硬化引起的心肌炎症和心肌细胞凋亡。此外,CD73的过表达通过上调腺苷受体A2A的表达来抑制NF-κB途径的激活。
■我们的研究表明，CD73/A2AR信号轴通过NF-κB通路的负反馈调节减轻肝硬化诱导的心肌炎症和凋亡。
