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XX sex chromosome complement promotes atherosclerosis in mice

Author

Listed:
  • Yasir AlSiraj

    (University of Kentucky)

  • Xuqi Chen

    (University of California)

  • Sean E. Thatcher

    (University of Kentucky)

  • Ryan E. Temel

    (University of Kentucky
    University of Kentucky)

  • Lei Cai

    (University of Kentucky
    University of Kentucky)

  • Eric Blalock

    (University of Kentucky)

  • Wendy Katz

    (University of Kentucky)

  • Heba M. Ali

    (University of Kentucky)

  • Michael Petriello

    (University of Kentucky, and Lexington Veterans Affairs Medical Center)

  • Pan Deng

    (University of Kentucky, and Lexington Veterans Affairs Medical Center)

  • Andrew J. Morris

    (University of Kentucky, and Lexington Veterans Affairs Medical Center)

  • Xuping Wang

    (University of California
    University of California
    University of California)

  • Aldons J. Lusis

    (University of California
    University of California
    University of California)

  • Arthur P. Arnold

    (University of California)

  • Karen Reue

    (University of California)

  • Katherine Thompson

    (University of Kentucky)

  • Patrick Tso

    (University of Cincinnati)

  • Lisa A. Cassis

    (University of Kentucky)

Abstract

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating a primary effect of sex chromosomes. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly are greater in XX male and female mice with higher intestinal lipids. Together, our results show that an XX sex chromosome complement promotes the bioavailability of dietary fat to accelerate atherosclerosis.

Suggested Citation

  • Yasir AlSiraj & Xuqi Chen & Sean E. Thatcher & Ryan E. Temel & Lei Cai & Eric Blalock & Wendy Katz & Heba M. Ali & Michael Petriello & Pan Deng & Andrew J. Morris & Xuping Wang & Aldons J. Lusis & Art, 2019. "XX sex chromosome complement promotes atherosclerosis in mice," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10462-z
    DOI: 10.1038/s41467-019-10462-z
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    Cited by:

    1. Peixiang Zhang & Joseph J. Munier & Carrie B. Wiese & Laurent Vergnes & Jenny C. Link & Fahim Abbasi & Emilio Ronquillo & Katherine Scheker & Antonio Muñoz & Yu-Lin Kuang & Elizabeth Theusch & Meng Lu, 2024. "X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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