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J Clin Lipidol. 2017 Sep - Oct;11(5):1192-1200.e3. doi: 10.1016/j.jacl.2017.06.018. Epub 2017 Jul 8.

Paradoxical coronary artery disease in humans with hyperalphalipoproteinemia is associated with distinct differences in the high-density lipoprotein phosphosphingolipidome.

Author information

1
National Institute for Health and Medical Reserch (INSERM), Research Unit 1166 ICAN, Paris, France; University of Pierre and Marie Curie - Paris 6, Paris, France; AP-HP, Groupe Hospitalier Pitié Salpétrière, Paris, France; ICAN Analytics, ICAN Institute, Paris, France; Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
ICANalytics, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital, Paris, France.
3
National Institute for Health and Medical Reserch (INSERM), Research Unit 1166 ICAN, Paris, France; University of Pierre and Marie Curie - Paris 6, Paris, France; AP-HP, Groupe Hospitalier Pitié Salpétrière, Paris, France; ICAN Analytics, ICAN Institute, Paris, France.
4
Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
5
National Institute for Health and Medical Reserch (INSERM), Research Unit 1166 ICAN, Paris, France; University of Pierre and Marie Curie - Paris 6, Paris, France; AP-HP, Groupe Hospitalier Pitié Salpétrière, Paris, France; ICAN Analytics, ICAN Institute, Paris, France. Electronic address: anatol.kontush@upmc.fr.
6
Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mcuchel@mail.med.upenn.edu.

Abstract

BACKGROUND:

Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with risk of coronary artery disease (CAD) in epidemiologic studies. Despite this, the directionality of this relationship and the underlying biology behind it remain to be firmly established, especially at the extremes of HDL-C levels.

OBJECTIVE:

We investigated differences in the HDL phosphosphingolipidome in a rare population of subjects with premature CAD despite high HDL-C levels to gain insight into the association between the HDL lipidome and CAD disease status in this unusual phenotype. We sought to assess differences in HDL composition that are associated with CAD in subjects with HDL-C >90th percentile. We predicted that quantitative lipidomic analysis of HDL particles would reveal novel differences between CAD patients and healthy subjects with matched HDL-C levels.

METHODS:

We collected plasma samples from 25 subjects with HDL-C >90th percentile and clinically manifest CAD and healthy controls with HDL-C >90th percentile and without self-reported CAD. More than 140 individual HDL phospholipid and sphingolipid species were analyzed by LC/MS/MS.

RESULTS:

Significant reductions in HDL phosphatidylcholine (-2.41%, Q value = 0.025) and phosphatidylinositol (-10.7%, Q value = 0.047) content, as well as elevated sphingomyelin (+10.0%, Q value = 0.025) content, and sphingomyelin/phosphatidylcholine ratio (+12.8%, P value = .005) were associated with CAD status in subjects with high HDL-C.

CONCLUSIONS:

These differences may lay the groundwork for further analysis of the relationship between the HDL lipidome and disease states, as well as for the development of biomarkers of CAD status and HDL function.

KEYWORDS:

Coronary artery disease; HDL; Hyperalphalipoproteinemia; Lipidomics; Phospholipids

PMID:
28826666
DOI:
10.1016/j.jacl.2017.06.018
[Indexed for MEDLINE]

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