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Increased aortic atherosclerotic plaque development in female apolipoprotein E-null mice is associated with elevated thromboxane A2 and decreased prostacyclin production

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Smith D. D., Tan X., Tawfik O., Milne G., Stechschulte D. J., Dileepan K. N.

Journal of Physiology and Pharmacology

2010

tom 61

nr 3

309-316

The production of thromboxane A2 (TXA2) and prostacyclin (prostaglandin I2, PGI2) is known to be increased in patients with atherosclerosis. In this study, we evaluated the influence of gender on TXA2 and PGI2 production, and their association with the progression of atherosclerosis in apolipoprotein E-null (ApoE-/-) mice maintained on a high fat diet for 3 months. En face analyses of aortas showed marked increases in plaque formation in female ApoE-/- mice. Quantification of the hematoxylin/eosin (H&E) stained cross sections of the aortic arch revealed 3 to 4-fold higher plaque thickness in female ApoE-/- mice. Analyses of 24-hours urine samples for 11-dehydro TXB2 and 2, 3-dinor-6-keto PGF1alpha indicated that female ApoE-/- mice produce up to 15-fold more TXA2 and 50% less PGI2 than the age matched males. Interestingly, the serum cholesterol levels in ApoE-/- females were 20% lower than males on the high fat regimen. No gender-associated changes in the number of T lymphocytes, mast cells and macrophages were evident in the lesion areas of ApoE-/- mice. The results suggest that the markedly elevated TXA2 production and reduced PGI2 production are gender-related proatherogenic risk factors in female ApoE-/- mice.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Dileepan K. N.

1 Milne G.

1 Smith D. D.

1 Stechschulte D. J.

1 Tan X.

1 Tawfik O.

1 2010

Wyniki wyszukiwania

Increased aortic atherosclerotic plaque development in female apolipoprotein E-null mice is associated with elevated thromboxane A2 and decreased prostacyclin production