Estrogen inhibits the initiation of fatty streaks throughout the vasculature but does not inhibit intra-plaque hemorrhage and the progression of established lesions in apolipoprotein E deficient mice

Estrogen has previously been shown to inhibit development of early atherosclerotic lesions in hyperlipidemic mice. However, it is still not known whether estrogen also inhibits progression and destabilization of lesions once established and whether there are other effects of long-term hormone therapy in mice. To address this question, male, 20-week old, apolipoprotein E deficient mice were administered 17-beta estradiol or placebo subcutaneously for between 4 and 40 weeks. Estrogen administration did not cause regression of established lesions in the carotid arteries, aortic arch and thoracic aorta but prevented the initiation of new lesions in the abdominal aorta and iliac, femoral and popliteal arteries. Although the established lesions were slightly smaller in the innominate artery of the estrogen treated mice, estrogen did not prevent lesion progression. Estrogen administration also had no effect on the frequency of intra-plaque hemorrhage, atrophy of the fibrous cap, medial erosion, and fibro-fatty nodules, but did reduce the frequency of fatty streaks that form on top of or adjacent to the established lesions in the innominate artery. These data suggest that estrogen inhibits the initiation of the fatty streak but does not alter the progression of established lesions through stages of instability and healing.