R. J. Torry

Angiogenesis in the uterus: potential regulation and relation to tumor angiogenesis.

ABSTRACT: Except under certain pathological conditions such as wound healing and solid tumor growth, angiogenesis is a relatively rare event in the adult. One exception, however, is the angiogenesis that occurs during the cyclical changes in the female reproductive tract. Many factors, chemical as well as mechanical, have been shown to be capable of promoting or inhibiting angiogenesis in vivo and in vitro. However, despite intense research efforts, the mechanisms involved in the regulation of angiogenesis in vivo are not fully understood. In this article we briefly review the basic steps involved in angiogenesis and present examples of factors and conditions that may serve as potential regulators of angiogenesis in the nonpregnant uterus. Finally, we discuss some of the architectural, anatomical, and physiological differences between the microcirculatory beds established during normal, self‐limited vessel growth and that associated with the uncontrolled, pathological vascular growth that accompanies tumor growth and metastasis.

Neovascularization of Embryonic Rat Hearts Cultured in oculo Closely Mimics in utero Coronary Vessel Development

Coronary neovascularization was studied following grafting of avascular hearts from gestation day-12 (E-12) rat embryos to the anterior eye chambers of adult rats. Volume densities (Vv) of vessels, myocytes, and the extracellular matrix (ECM) after 3-7, 14, 21, and 35 days in oculo were compared to Vv in hearts developing in utero at E-15, E-18, and E-20. The myocardium in both models exhibited similar vessel Vv and capillary developmental stages: (1) clustering of endothelial cells and red blood cells; (2) endothelial cell migration, and (3) tube formation/maturation. The Vv of myocytes increased while that of the ECM remained constant over time. Cross-species grafting utilizing species-specific antibodies determined that the majority, but not all, of the 10-day graft vasculature was of graft origin. Therefore, both de novo growth (vasculogenesis) and sprouting (angiogenesis) were occurring in oculo. Tracer molecules infused into host rats reached the outermost graft vessels only after 10 days in oculo, suggesting a functional link with the host circulation after this time. Thus, we have shown that both models exhibit similar: (1) vascular Vv; (2) shifts in Vv of nonvascular components; (3) stages of neovascularization, and (4) mechanisms of neovascularization. In conclusion, coronary neovascularization occurring in oculo closely mimics normal coronary vessel development.