Angiogenesis is a multistep process by which new blood vessels are formed from existing blood vessels.26-100 It is a highly regulated process and essential for reproduction, morphogenesis, development, and wound repair.101102 Angiogenesis is also critical for patients with coronary
artery diseases in order to maintain blood flow to bypass the blocked coronary artery and protect from heart ischemia and attacks. Uncontrolled and persistent changes in the angiogenic process "switch" can occur at different stages of tumor progression, depending on tumor type and the surrounding environment.103 Physiological and pathophysiological angiogenesis can be regulated by various positive and negative regulators, including vascular endothelial growth factor (VEGF), fibroblast growth factors (FGFs), platelet-derived growth factors (PDGFs), epidermal growth factors (EGFs), thrombospondin-1 (TSP-1) and various types of statins, and inhibitors of HMG-Co and A-reductase.103 Although, the molecular mechanisms associated with physiological and pathophysiological angiogenesis have not been fully elucidated, it is assumed that angiogenesis is the result of imbalanced expression and function of positive and negative regulators.103105 The angiogenic switch induced by imbalanced functions of positive and negative regulators can be modulated by various internal and external stimuli.106
In healthy adults, angiogenesis is a quiescent process, with the exception that in the female reproductive tract, this event is modulated in each menstrual cycle in response to the estrogen level in the blood. In premenopausal women, estrogen promotes angiogenesis in association with some diseases like Takayasu's arteritis and lupus erythematous.27 Together, the studies indicate that angiogenesis can be regulated by estrogen. A role for estrogen in angiogenesis is further supported by our studies on the rat pituitary that indicated estrogen as the sole etiological agent for the development of tumor angiogenesis during the development of estrogen-induced tumorigenesis.13 Some additional observations, such as inhibition of angiogenesis by antiestrogens, also support estrogen as a positive regulator of angiogenesis.107110
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