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XX sex chromosome complement promotes atherosclerosis in mice.
Authors AlSiraj Y, Chen X, Thatcher SE, Temel RE, Cai L, Blalock E, Katz W, Ali HM,
Petriello M, Deng P, Morris AJ, Wang X, Lusis AJ, Arnold AP, Reue K, Thompson K,
Tso P, Cassis LA
Submitted By Submitted Externally on 8/6/2019
Status Published
Journal Nature communications
Year 2019
Date Published 6/1/2019
Volume : Pages 10 : 2631
PubMed Reference 31201301
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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