XX sex chromosome complement promotes atherosclerosis in mice

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, Arthur P. Arnold, Karen Reue, Katherine Thompson, Patrick Tso and Lisa A. Cassis ()
Additional contact information
Yasir AlSiraj: University of Kentucky
Xuqi Chen: University of California
Sean E. Thatcher: University of Kentucky
Ryan E. Temel: University of Kentucky
Lei Cai: 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
Aldons J. Lusis: 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

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10462-z

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