Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density

Uterine leiomyomas are the most prevalent benign tumor type in women of rep roductive age and are one of the most common indications for hysterectomy. The expression of five angiogenic factors, adrenomedullin (ADM), vascular e ndothelial growth factor (VEGF), acidic fibroblast growth factor, basic fib roblast growth factor, and platelet-derived endothelial cell growth factor/ thymidine phosphorylase, were examined in 91 uteri collected throughout the menstrual cycle; 52 of which contained leiomyomata, and the remainder were normal controls. The microvascular density and endothelial proliferative i ndices were then determined for each of the uterine sections. ADM and VEGF were the most widely expressed angiogenic factors in the leiomyomas. Furthe rmore, the expression of ADM and VEGF in the endometrium and myometrium was up-regulated in leiomyoma-bearing uteri compared with controls. Although a cidic fibroblast growth factor and basic fibroblast growth factor were expr essed in leiomyomas and endometrium in all of the uterine samples examined, they were only expressed in the myometrium of leiomyomata-bearing uteri, E ndothelial proliferation in leiomyomas was statistically greater than that of the myometrium and endometrium, both within and between uteri (P < 0.05) , The vascular density in the myometrium but not the endometrium was signif icantly increased in leiomyoma-containing uteri (P < 0.05), Expression of A DM alone correlated directly with vascular density and endothelial cell pro liferation index in leiomyomas and myometrium and may account for the high vascularity found in leiomyomas and the myometrium of leiomyoma-bearing ute ri, As such, ADM is identified as a novel target for antiangiogenic therapy of these benign, clinically problematic uterine tumors.