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Pulmonary gas transfer related to markers of angiogenesis during the menstrual cycle

¹Department of Pulmonary, Allergy, and Critical Care Medicine and ²Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; and ³Division of Cardiology, Northwestern Memorial Hospital, Chicago, Illinois

Submitted 7 June 2007 ; accepted in final form 15 August 2007

Gas transfer in the female lung varies over the menstrual cycle in parallel with the cyclic angiogenesis that occurs in the uterine endometrium. Given that vessels form and regress in the uterus under the control of hormones, angiogenic factors, and proangiogenic circulating bone marrow-derived progenitor cells, we tested the possibility that variation in pulmonary gas transfer over the menstrual cycle is related to a systemic cyclic proangiogenic state that influences lung vascularity. Women were evaluated over the menstrual cycle with weekly measures of lung diffusing capacity and its components, the pulmonary vascular capillary bed and membrane diffusing capacity, and their relation to circulating CD34⁺CD133⁺ progenitor cells, hemoglobin, factors affecting hemoglobin binding affinity, and proangiogenic factors. Lung diffusing capacity varied over the menstrual cycle, reaching a nadir during the follicular phase following menses. The decline in lung diffusing capacity was accounted for by 25% decrease in pulmonary capillary blood volume. In parallel, circulating CD34⁺CD133⁺ progenitor cells decreased by 24% and were directly related to angiogenic factors and to lung diffusing capacity and pulmonary capillary blood volume. The finding of a greater number of lung microvessels in ovariectomized female mice receiving estrogen compared with placebo verified that pulmonary vascularity is influenced by hormonal changes. These findings suggest that angiogenesis in the lungs may participate in the cyclic changes in gas transfer that occur over the menstrual cycle.

endothelial progenitor cell