TLR4型
糖尿病性心肌病
炎症
化学
心房颤动
链脲佐菌素
受体
内科学
纤维化
细胞凋亡
内分泌学
医学
糖尿病
心肌病
心力衰竭
生物化学
作者
Tiefeng Shi,Guangji Wang,Jianye Peng,Manhua Chen
出处
期刊:Pharmacology
[S. Karger AG]
日期:2023-01-01
卷期号:108 (4): 311-320
摘要
Introduction: Myeloid differentiation protein 1 (MD1), a negative regulator of toll-like receptor 4 (TLR4), is widely expressed in the heart. Recent studies have shown that MD1 plays an important role in cardiac remodelling. However, the effects and potential mechanisms underlying MD1-mediated atrial remodelling in diabetic cardiomyopathy (DCM) remain unclear. Therefore, this study was designed to explore the role of MD1 in DCM-related atrial remodelling. Methods: MD1 knockout (MD1-KO) mice and wild-type (WT) littermates were injected with streptozotocin (STZ) to establish a diabetic mouse model. These mice were then used to evaluate MD1 expression and its effects on atrial remodelling in vivo. Results: MD1 expression was significantly decreased in STZ-induced diabetic mice. The loss of MD1 aggravated atrial fibrosis, inflammation, and apoptosis in DCM mice and promoted atrial remodelling. MD1-KO diabetic mice also showed higher susceptibility to atrial fibrillation (AF) and worse cardiac function. Mechanistically, the deletion of MD1 promoted the activation of the TLR4/NF-κB signalling pathway, resulting in atrial remodelling in DCM mice via increased p65 phosphorylation. Conclusions: The deletion of MD1 plays an important role in inflammatory and apoptotic atrial remodelling and increases susceptibility to AF in DCM mice, providing a new target for the preventive treatment of DCM-related atrial remodelling.
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