XX sex chromosome complement promotes atherosclerosis in mice.

Autor: AlSiraj Y; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, 40536, KY, USA., Chen X; Integrative Biology and Physiology, University of California, Los Angeles, 90095, CA, USA., Thatcher SE; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, 40536, KY, USA., Temel RE; Saha Cardiovascular Research Center, University of Kentucky, Lexington, 40536, KY, USA.; Department of Physiology, University of Kentucky, Lexington, 40536, KY, USA., Cai L; Saha Cardiovascular Research Center, University of Kentucky, Lexington, 40536, KY, USA.; Department of Physiology, University of Kentucky, Lexington, 40536, KY, USA., Blalock E; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, 40536, KY, USA., Katz W; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, 40536, KY, USA., Ali HM; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, 40536, KY, USA., Petriello M; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Kentucky, and Lexington Veterans Affairs Medical Center, Lexington, 40536, KY, USA., Deng P; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Kentucky, and Lexington Veterans Affairs Medical Center, Lexington, 40536, KY, USA., Morris AJ; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Kentucky, and Lexington Veterans Affairs Medical Center, Lexington, 40536, KY, USA., Wang X; Department of Microbiology, Immunology & Molecular Genetics, Human Genetics, College of Medicine, University of California, Los Angeles, 90095, CA, USA.; Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 90095, CA, USA.; Human Genetics, University of California, Los Angeles, 90095, CA, USA., Lusis AJ; Department of Microbiology, Immunology & Molecular Genetics, Human Genetics, College of Medicine, University of California, Los Angeles, 90095, CA, USA.; Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 90095, CA, USA.; Human Genetics, University of California, Los Angeles, 90095, CA, USA., Arnold AP; Integrative Biology and Physiology, University of California, Los Angeles, 90095, CA, USA., Reue K; Human Genetics, University of California, Los Angeles, 90095, CA, USA., Thompson K; Department of Statistics, University of Kentucky, Lexington, 40536, KY, USA., Tso P; Department of Pathology, University of Cincinnati, Cincinnati, 45215, OH, USA., Cassis LA; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, 40536, KY, USA. lcassis@uky.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Jun 14; Vol. 10 (1), pp. 2631. Date of Electronic Publication: 2019 Jun 14.
DOI: 10.1038/s41467-019-10462-z
Abstrakt: 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.
Databáze: MEDLINE