Abstract

Cardiovascular diseases are often associated with impaired lipid metabolism. Animal models are useful for deciphering the physiological mechanisms underlying these pathologies. However, lipid metabolism is contrasted between species limiting the transposition of findings from animals to human. Hence, we aimed to compare extended lipid profiles of several animal species to bring new insights in animal model selections. Human lipid phenotype was compared with those of 10 animal species. Standard plasma lipids and lipoprotein profiles were obtained by usual methods and lipidomic analysis was conducted by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). As anticipated, we found contrasted lipid profiles between species. Some of them exhibited similar plasma lipids to human (non-human primate, rat, hamster, pig), but only usual lipid profiles of pigs were superimposable with human. LC-HRMS analyses allowed the identification of 106 other molecular species of lipids, common to all samples and belonging to major lipid families. Multivariate analyses clearly showed that hamster and, in a lower extent mouse, exhibited close lipid fingerprints to that of human. Besides, several lipid candidates that were previously reported to study cardiovascular diseases ranged similarly in human and hamster. Hence, hamster appeared to be the best option to study physiological disturbances related to cardiovascular diseases.

Highlights

  • Atherothrombotic cardiovascular diseases (ACVD) are the leading cause of death worldwide and are widely associated with lipid disturbances[1,2,3]

  • We aimed to investigate both global and specific lipid profiles in those species to create global lipid fingerprints and assess the similarity and differences compared with humans

  • An unsupervised Principal component analysis (PCA) model was applied to get an overview of variance between lipid profiles of species (Fig. 2)

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Summary

Introduction

Atherothrombotic cardiovascular diseases (ACVD) are the leading cause of death worldwide and are widely associated with lipid disturbances[1,2,3]. Lipoprotein metabolism and vascular physiology are often contrasted between species limiting the transposition of findings from animals to human[4,5] Such differences should be considered for animal model selection and for data understanding within a realistic extrapolation framework for a better assessment of disturbances involved in humans[6]. Glycerophospholipids and sphingolipids have been shown to be significantly altered during the atherosclerotic progression in apoE−/− mice[8], and other studies showed that elevated concentrations of lysophosphatidylcholines (LPC) and sphingomyelins (SM) were correlated with atherosclerosis development[9,10] These findings have been recently supported by human prospective ACVD outcome studies[11]. We explored an extended lipid profile of nine animal species including non-human primate, dog, cat, pig, horse, bovine, hamster, mouse and rat along with human Some of these species were already described as potential models for human ACVD12. We aimed to investigate both global (non-targeted) and specific (targeted) lipid profiles in those species to create global lipid fingerprints and assess the similarity and differences compared with humans

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