Abstract 1097: Very-low Dose Endotoxemia Induces High Density Lipoprotein Remodeling and Reduces Cholesterol Efflux in the Absence of a Clinical Inflammatory Response

Autor: Sean P Heffron, Nehal N Mehta, Margarita de la Llera-Moya, Karen Terembula, Christine Hinkle, Megan Wolfe, Muredach P Reilly
Rok vydání: 2007
Předmět:
Zdroj: Circulation. 116
ISSN: 1524-4539
0009-7322
Popis: Introduction: Chronic low-grade inflammation is thought to induce atherogenic changes in HDL function. Indeed, we have demonstrated HDL particle remodeling during experimental human endotoxemia (3ng/kg). However, this model is associated with marked clinical symptoms, and may not reflect the chronic low-grade inflammation characteristic of insulin resistant atherogenic states. Hypothesis: We hypothesized that very low-dose human endotoxemia (LPS; 0.6ng/kg) induces sub-clinical inflammation causing changes in HDL composition and function, without generating measurable clinical responses. Methods: Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8) were randomized to separate 36-hour inpatient visits (placebo versus intravenous LPS 0.6ng/kg) in a double-masked, placebo-controlled, crossover study. Serial plasma and serum samples were collected for measurement of cytokines, acute phase reactants, lipids and lipoproteins. Ex-vivo 3 H-cholesterol efflux from FU5AH cells (SR-BI model) to the HDL fraction from serum, serially isolated during placebo/endotoxemia, was examined (N=5). Repeated measures ANOVA was applied to the data. Results: There was no significant difference between placebo and LPS in the clinical measures of inflammatory response, including body temperature and heart rate. Relative to placebo, LPS produced a peak 20-fold increase in TNFα (p = 0.01) and a 15-fold increase in CRP (p Conclusions: A very low-dose of endotoxin produces relatively low-grade innate immune responses, without clinical symptoms, but with significant changes in HDL composition and function. This study provides evidence that a modest inflammatory response, consistent with chronic inflammation in atherogenic states in vivo , induces atherogenic changes in HDL.
Databáze: OpenAIRE
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