Accelerated atherosclerosis and premature calcified cartilaginous metaplasia in the aorta of diabetic male Apo E knockout mice can be prevented by chronic treatment with 17 beta-estradiol

Epidemiological data indicate that estrogens significantly reduce the risk of morbidity and mortality due to cardiovascular diseases in postmenopausal women. Although numerous animal studies demonstrated inhibition of early a theromatous lesion formation by estrogen treatment in several species, info rmation about the potential benefits of estrogens on complex, advanced athe rosclerotic lesions is still lacking. The present study was designed to tes t whether chronic treatment with 17 beta-estradiol affects hyperglycemia-in duced premature advanced lesion formation in 40-week-old-male apolipoprotei n E-deficient (Apo E-KO) mice. In order to accelerate advanced lesion forma tion, we treated male Apo E-KO mice with streptozotocin (STZ) at the age of 6 weeks. Two weeks later the STZ-treated mice received a slow release pell et containing either 17 beta-estradiol or placebo. STZ treatment caused sus tained hyperglycemia without changes in serum total cholesterol or triglyce ride levels compared to citrate control mice. STZ-treated Apo E-KO mice dev eloped significantly more lesions in some (but not all) parts of the aorta and its main branches, and caused premature calcified cartilaginous metapla sia in the lesions of the proximal aorta. Chronic treatment with 17 beta-es tradiol lead to a significant decrease in blood glucose and triglyceride le vels, reduced the lesion area in all vascular segments studied and prevente d cartilaginous metaplasia in STZ-treated Apo E-KO mice. The results of thi s study show that STZ treatment leads to significant acceleration of athero sclerotic lesion formation and premature occurrence of calcified cartilagin ous areas in Apo E-KO mice, which could be effectively prevented by chronic estrogen treatment. (C) 1999 Published by Elsevier Science Ireland Ltd. Al l rights reserved.