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; Lisa A. Cassis

doi:10.1038/s41467-019-10462-z

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, Lisa A. Cassis

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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.

Original language	English
Article number	2631
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10462-z
State	Published - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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AlSiraj, Y., Chen, X., Thatcher, S. E., Temel, R. E., Cai, L., Blalock, E., Katz, W., Ali, H. M., Petriello, M., Deng, P., Morris, A. J., Wang, X., Lusis, A. J., Arnold, A. P., Reue, K., Thompson, K., Tso, P., & Cassis, L. A. (2019). XX sex chromosome complement promotes atherosclerosis in mice. Nature Communications, 10(1), Article 2631. https://doi.org/10.1038/s41467-019-10462-z

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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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AU - AlSiraj, Yasir

AU - Chen, Xuqi

AU - Thatcher, Sean E.

AU - Temel, Ryan E.

AU - Cai, Lei

AU - Blalock, Eric

AU - Katz, Wendy

AU - Ali, Heba M.

AU - Petriello, Michael

AU - Deng, Pan

AU - Morris, Andrew J.

AU - Wang, Xuping

AU - Lusis, Aldons J.

AU - Arnold, Arthur P.

AU - Reue, Karen

AU - Thompson, Katherine

AU - Tso, Patrick

AU - Cassis, Lisa A.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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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XX sex chromosome complement promotes atherosclerosis in mice

Abstract

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