Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases
Year: 2014
Type: review
Abstract: 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.
Authors: Parth N. Patel, Rhia Y. Shah, Jane F. Ferguson, Muredach P. Reilly
Institutions: Vanderbilt University, University of Pennsylvania
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Mentored Patient Oriented Research in Cardiometabolic Disease, G1702535744, Glycomics of Heart and Lung Disease in the Genomic Era, Elucidation of Tissue-Specific Transcriptomic Profiles in Cardio-metabolic Disease, Fractalkine in Adipose Inflammation and Insulin Resistance, G6892940000, Lipids as Modulators of the Response to Vascular Injury
OpenAlex ID: W2159728803