Sex does not seem to influence the formation of aortic lesions in the P-407-induced mouse model of hyperlipidemia and atherosclerosis.
Coronary heart disease secondary to atherosclerosis is the leading cause of death for men in the United States. Using a new, nontransgenic, non-fat-fed mouse model of hyperlipidemia and atherosclerosis developed in our laboratory, we investigated the effect of sex on lipid profiles and subsequent aortic atherosclerotic lesion formation. Female and male C57BL/6 mice, which consumed a low-fat diet, were treated with either normal saline or poloxamer 407 (P-407), a triblock copolymer comprised of poly(oxyethylene) and poly(oxypropylene) units, for 4 months. Blood samples were obtained at 0, 1, 2, 3, and 4 months, whereas hearts and livers were harvested only at 4 months, because this model requires approximately 4 months for significant atheroma formation. P-407-treated mice of either sex demonstrated a profound increase in plasma cholesterol and triglyceride; at 3 and 4 months the plasma lipids were significantly (p < 0.05) higher for male mice compared with female mice. Aortas retrieved from P-407-treated mice of either sex after 4 months demonstrated a significant (p < 0.001) increase in the mean atherosclerotic lesion size compared with their respective saline-treated controls, but there was no significant (p > 0.05) difference between lesion sizes for P-407-treated male mice (1.02 +/- 0.074 x 10(5) microm(2)) compared with P-407-treated female mice (1.14 +/- 0.28 x 10(5) microm(2)). Livers harvested at 4 months from either sex of P-407-treated mice displayed no damage to hepatocytes but increased proliferation of macrophages (Kupffer cells), which contained sequestered lipids. Thus, male C57BL/6 mice form atherosclerotic lesions as extensive as female mice in the P-407 mouse model of atherosclerosis.
Johnston
Thomas P
TP
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, Kansas City, MO 64110-2499, USA. Johnsont@umkc.edu
Coker
James W
JW
Paigen
Beverly J
BJ
Tawfik
Ossama
O
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D018752:Diet, Fat-Restricted; D005260:Female; D005487:Foam Cells / Q000378:metabolism; D006099:Granuloma / Q000209:etiology; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020442:Poloxamer; D012737:Sex Factors; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D014280:Triglycerides; D020442:Poloxamer; D002784:Cholesterol