Chronic vascular pathogenesis results in the reduced serum Metrnl levels in ischemic stroke patients  

作　　者：Zhu-wei Miao Nuo Wang Wen-jun Hu Si-li Zheng Dong-sheng Wang Fu-qiang Chang Zhi Wang Jia-sheng Tian Xiao-hui Dong Tao Wu Chao-yu Miao 

机构地区：[1]Department of Pharmacology,Second Military Medical University/Naval Medical University,Shanghai,200433,China [2]Department of Neuroloy and Neurovascular Center,The First Affiliated Hospital(Changhai Hospital),Second Military Medical University/Naval Medical University,Shanghai,200433,China [3]Department of Pharmacy,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,200120,China

出　　处：《Acta Pharmacologica Sinica》2024年第5期914-925,共12页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China Major Project(82030110,82330117 and 81730098 to CYM).

摘　　要：Metrnl is a secreted protein involved in neurite outgrowth,insulin sensitivity,immunoinflammatory responses,blood lipids and endothelial protection.In this study,we investigated the role of Metrnl in ischemic stroke.Fifty-eight ischemic stroke patients(28 inpatient patients within 2 weeks of onset and 30 emergency patients within 24 h of onset)and 20 healthy controls were enrolled.Serum Metrnl was measured by enzyme-linked immunosorbent assay.We showed that serum Metrnl levels were significantly reduced in both inpatient and emergency patient groups compared with the controls.Different pathological causes for ischemic stroke such as large artery atherosclerosis and small artery occlusion exhibited similar reduced serum Metrnl levels.Transient ischemic attack caused by large artery atherosclerosis without brain infarction also had lower serum Metrnl levels.Metrnl was correlated with some metabolic,inflammatory and clotting parameters.Reduced serum Metrnl was associated with the severity of intracranial arterial stenosis and the presence of ischemic stroke.In order to elucidate the mechanisms underlying the reduced serum Metrnl levels,we established animal models of ischemic stroke in normal mice,atherosclerotic apolipoprotein E-knockout mice and Metrnl-knockout mice by middle cerebral artery occlusion(MCAO)using intraluminal filament or electrocoagulation.We demonstrated that serum Metrnl levels were significantly lower in atherosclerosis mice than normal mice,whereas acute ischemic stroke injury in normal mice and atherosclerosis mice did not alter serum Metrnl levels.Metrnl knockout did not affect acute ischemic stroke injury and death.We conclude that reduced serum Metrnl levels are attributed to the chronic vascular pathogenesis before the onset of ischemic stroke.Metrnl is a potential target for prevention of ischemic stroke.

关 键 词：ischemic stroke Metrnl secreted protein vascular pathogenesis ATHEROSCLEROSIS THROMBUS 

分 类 号：R743.3[医药卫生—神经病学与精神病学]