XX sex chromosome complement promotes atherosclerosis in mice

Yasir Alsiraj(University of Kentucky), Xuqi Chen(University of California, Los Angeles), Sean E. Thatcher(University of Kentucky), Ryan E. Temel(University of Kentucky), Lei Cai(University of Kentucky), Eric M. Blalock(University of Kentucky), Wendy S. Katz(University of Kentucky), Heba Ali(University of Kentucky), Michael C. Petriello(University of Kentucky), Pan Deng(University of Kentucky), Andrew J. Morris(University of Kentucky), Xuping Wang(University of California, Los Angeles), Aldons J. Lusis(University of California, Los Angeles), Arthur P. Arnold(University of California, Los Angeles), Karen Reue(University of California, Los Angeles), Katherine Thompson(University of Kentucky), Patrick Tso(University of Cincinnati), Lisa A. Cassis(University of Kentucky)
Nature Communications
June 14, 2019
10.1038/s41467-019-10462-z
Cited by 287Open Access
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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.

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