Abstract

Atherosclerosis is a chronic inflammatory disease that is caused by the accumulation of LDL particles in the intima, causing the activation of immune cells and triggering an inflammatory response. LPS is a potent activator of the innate immune response and it can be transported by lipoproteins. Since humans are much more sensitive to LPS than other mammals, and very low amounts of LPS can elicit an immune response, the aim of this study is to characterize the distribution of LPS and its immunogenic portion (3OHFAs) among lipoprotein types of healthy men. We separated lipoprotein fractions by ultracentrifugation and the amount of each 3OHFA was measured by MS in each lipoprotein fraction to calculate LPS concentration. Lipoprotein particle concentration was measured by NMR. LDL and HDL fractions transported the highest concentration of LPS (35.7% and 31.5%, respectively), but VLDL particles carried more LPS molecules per particle (0.55 molecules/particle) than LDL or HDL (p < 0.01). The distribution of LPS and all 3OHFAs among lipoprotein fractions showed high interindividual variability, suggesting that they may be studied as a potential biomarker. This may help understand the role of LPS in atherosclerosis in those cases where the disease cannot be explained by traditional risk factors.

Highlights

  • Atherosclerosis is a chronic inflammatory condition resulting from arterial haemodynamic changes and complex interactions between a variety of cell types, lipids and soluble mediators [1]

  • Atherosclerosis is an inflammatory process of the artery that leads to cholesterol accumulation and cardiovascular disease

  • We hypothesized that LPS may help to explain accelerated atherosclerosis, and the reason for this is threefold: (1) LPS binds to lipoproteins for its elimination; lipoproteins located in the subendothelial space may contain

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Summary

Introduction

Atherosclerosis is a chronic inflammatory condition resulting from arterial haemodynamic changes and complex interactions between a variety of cell types, lipids and soluble mediators [1]. Many risk factors for atherosclerosis have been identified, such as the relative amount of each lipoprotein type in plasma, familial history, systemic inflammation, a high-fat diet, tobacco and infections [2]. The etiopathology of atherosclerosis is complex, and the potential roles of several other factors have not yet been elucidated. Between 30% and 40% of complications derived from atherosclerosis occur in the absence of these risk factors, meaning that other still unknown causes may be involved. Identifying these other risk factors and their role could help understand the development and outcome of atherosclerosis in people where the traditional risk factors 4.0/).

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