背景:近年来肥胖增加,对糖尿病和其他合并症有影响。因此,3名糖尿病患者中有1名患有心血管疾病(CVD)。葡萄糖之间的网络,免疫系统,内皮和心外膜脂肪在动脉粥样硬化的促炎和血栓形成机制中具有重要作用。自从塞马鲁肽以来,长效胰高血糖素样肽1-受体激动剂(GLP-1-RA),一种降糖药物,减轻体重,我们旨在研究其对人体心外膜脂肪(EAT)的影响,主动脉内皮细胞和中性粒细胞作为动脉粥样硬化参与心血管细胞。
方法:收集心脏手术患者的EAT和皮下脂肪(SAT)。脂肪释放外泌体的葡萄糖消耗和蛋白质负荷差异,司马鲁肽或/和胰岛素治疗后,通过酶和TripleTOF分析,分别。通过流式细胞术和功能荧光分析来分析人嗜中性粒细胞表型及其与主动脉内皮细胞(HAEC)或血管生成的粘附。在使用司马鲁肽治疗6个月之前和之后,通过流式细胞术和Luminex-multiplex测定了患者的免疫细胞和血浆蛋白标志物。
结果:GLP-1受体在脂肪和中性粒细胞上表达。semaglutide处理后,在EAT外植体上鉴定出差异的外泌体-蛋白质货物。这种药物增加了凝溶胶蛋白的分泌,抗血栓蛋白,吃,调节CD11b对中性粒细胞,它的迁移和内皮粘附,由肥胖蛋白诱导,FABP4或化学引诱物。单核细胞和中性粒细胞表型和血浆肥胖,伸展,间皮,纤维化,接受司马鲁肽治疗6个月的患者的炎症标志物显示,FABP4水平降低20%,具有统计学意义,中性粒细胞-CD88增加80%.
结论:塞马鲁肽增加心外膜脂肪的内分泌活性,具有抗血栓形成的特性。此外,这种药物调节由肥胖标记物诱导的促炎和动脉粥样硬化特征,FABP4在司马鲁肽治疗后也降低。
Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells.
EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide.
GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88.
Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment.