Storm of Cardiovascular Markers After LPS Administration in Human Volunteers

Abstract

Acute infections are associated with an elevated cardiovascular risk. However, little is known about the interactions of acute inflammatory responses and the cardiovascular system. We therefore aimed to evaluate effects of acute inflammatory stimuli mediated by LPS administration on a set of 89 cardiovascular biomarkers. A single-blinded, placebo-controlled cross-over study using the human endotoxin model was performed. Ten healthy men were administered lipopolysaccharide (LPS) or placebo on two different study days after an overnight fast. Eighty-nine different cardiovascular biomarkers were measured repetitively over 48 h. Out of 89 cardiovascular biomarkers, 54 markers were significantly influenced by LPS infusion. The observed biomarker response to inflammation was more pronounced and complex than anticipated. In conclusion, our data show that the cardiovascular system is under enormous distress in response to experimental low-dose inflammation in humans, as demonstrated by a significant effect on 54 of the 89 biomarkers tested.

Keywords: Biomarker; Cardiovascular; Human endotoxin model; Infection lipopolysaccharide (LPS); Inflammation; Proximity extension assay (PEA).

Fig. 1

Cardiovascular biomarkers following placebo or LPS infusion. All parameters marked with “*” show significant differences after LPS infusion in comparison to placebo. Biomarkers were measured in NPX values (normalized protein expression), which is an arbitrary unit on a log-2 scale. Of note, values on the y-axis do not depict the NPX values but ratio-to-baseline in order to show the relative changes in a normalized manner. This means that changes on the logarithmic NPX scale are much larger than they appear in this graph. Parameters marked with “*” are significantly influenced by the administration of LPS in comparison to placebo

Fig. 2

Significant effects of LPS on cardiovascular biomarkers, showing number of affected markers per group