Angiogenesis inhibitors are administered to patients in an amount effective to regulate normal, non-transformed vascularized tissue size and/or growth by regulating its vascular compartment. Examples of tissues that can be controlled include adipose tissue, intestinal polyps, muscle (including cardiac) tissue, and endometrial tissue. The response of these tissues to the angiogenesis inhibitors is dose-dependent, reversible, and common to a variety of different angiogenesis inhibitors (examples use TNP-470, angiostatin, and endostatin), based on studies in animal models of obesity, intestinal polyps, cardiac hypertrophy, and endometriosis. Initial studies conducted in an adipose tissue model (genetically obese mice and normal control mice) showed that the growth and mass of adipose tissue is under the control of microvascular endothelium. Expansion of adipose tissue was associated with endothelial cell proliferation. Inhibition of angiogenesis led to reduction in adipose tissue mass. Weight gain in animals receiving angiogenesis inhibitors was significantly restricted, in spite of increases in appetite sufficient to cause weight gain in paired-fed mice. Discontinuation of the inhibitor resulted in rapid expasion of the adipose tissue. The effect was dose-dependent, repeatedly reversible, and occurred in response to all of the inhibitors tested. Significant inhibition was also observed in both the intestinal polyp and cardiac hypertrophy animal models, using dosages of two-thirds or less than the dosages used to treat tumors. Preliminary results in an endometriosis model also show a clear trend towards decreased development of endometriosis in animals treated with angiogenesis inhibitors at a dosage of one-third the dosage used to treat tumors. No effect on normal tissue that was not proliferating, other than adipose tissue, was observed.

 
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