Patel Parth N, Shah Rhia Y, Ferguson Jane F, Reilly Muredach P
From the Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (P.N.P., R.Y.S., M.P.R.); and Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (J.F.F.).
Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):525-34. doi: 10.1161/ATVBAHA.114.304455. Epub 2014 Dec 30.
Inflammation is a fundamental feature of several complex cardiometabolic diseases. Indeed, obesity, insulin resistance, metabolic dyslipidemia, and atherosclerosis are all closely linked inflammatory states. Increasing evidence suggests that the infectious, biome-related, or endogenous activation of the innate immune system may contribute to the development of metabolic syndrome and cardiovascular disease. Here, we describe the human experimental endotoxemia model for the specific study of innate immunity in understanding further the pathogenesis of cardiometabolic disease. In a controlled, experimental setting, administration of an intravenous bolus of purified Escherichia coli endotoxin activates innate immunity in healthy human volunteers. During endotoxemia, changes emerge in glucose metabolism, lipoprotein composition, and lipoprotein functions that closely resemble those observed chronically in inflammatory cardiovascular disease risk states. In this review, we describe the transient systemic inflammation and specific metabolic consequences that develop during human endotoxemia. Such a model provides a controlled induction of systemic inflammation, eliminates confounding, undermines reverse causation, and possesses unique potential as a starting point for genomic screening and testing of novel therapeutics for treatment of the inflammatory underpinning of cardiometabolic disease.
炎症是几种复杂的心脏代谢疾病的基本特征。事实上，肥胖、胰岛素抵抗、代谢性血脂异常和动脉粥样硬化都是密切相关的炎症状态。越来越多的证据表明，先天性免疫系统的感染性、生物群落相关或内源性激活可能促成代谢综合征和心血管疾病的发展。在此，我们描述了人类实验性内毒素血症模型，用于在进一步理解心脏代谢疾病发病机制时对先天性免疫进行特异性研究。在可控的实验环境中，静脉推注纯化的大肠杆菌内毒素可激活健康人类志愿者的先天性免疫。在内毒素血症期间，葡萄糖代谢、脂蛋白组成和脂蛋白功能会出现变化，这些变化与在炎症性心血管疾病风险状态下长期观察到的变化非常相似。在本综述中，我们描述了人类内毒素血症期间发生的短暂全身性炎症和特定代谢后果。这样一个模型可实现全身性炎症的可控诱导，消除混杂因素，排除反向因果关系，并具有作为基因组筛查和测试治疗心脏代谢疾病炎症基础的新型疗法的独特潜力。
