Effects of Pregnancy and Physical Activity on Angiogenesis and Endothelial Function: Implications for the Development of Preeclampsia
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Prospective epidemiological studies indicate that regular exercise during the year prior to conception reduces preeclampsia risk, whereas exercise during affects pregnancy reduces preeclampsia risk only at specific dosages, or in specific subpopulations. The risk of severe preeclampsia is increased among women who exercise for more than 270 minutes/week in early pregnancy. Physiology studies are needed to identify mechanisms through which regular exercise may influence preeclampsia risk. This dissertation examined the effects of pregnancy (30-36 weeks gestation), and regular exercise participation, on two important pathophysiological features of preeclampsia; circulating anti-angiogenic markers, represented by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and endothelial dysfunction. The results demonstrate that regularly exercising, pregnant non-smoking women have higher levels of serum placental growth factor (PlGF), lower levels of serum sFlt-1 and sFlt-1:PlGF, and are less likely to experience high serum sEng levels, than sedentary women. The effects of exercise on PlGF and sFlt-1:PlGF are more pronounced among women exercising less than 270 minutes/week in pregnancy. Anti-angiogenic changes that could contribute to preeclampsia were not observed immediately after short-duration, moderate-intensity exercise in the third trimester. Flow-mediated dilation (FMD) and the shear stimulus for FMD are not affected by pregnancy, however the time to peak FMD was increased in pregnancy. Regular exercise did not affect FMD or its shear stimulus in healthy pregnant or non-pregnant women. FMD and its shear stimulus were positively correlated in active, but not inactive, pregnant and non-pregnant women. Pregnancy and physical activity do not affect radial artery low flow-mediated constriction (L-FMC). L-FMC is artery dependent, occurring in the radial, but not the brachial, artery of healthy pregnant and non-pregnant women. The positive correlation between L-FMC and FMD suggests that L-FMC and FMD are not independent measurements. The results of this thesis suggest that physical activity and exercise may reduce preeclampsia risk by reducing concentrations of angiogenic markers. Although exercise participation did not affect conduit artery vascular function in healthy pregnant women, future studies should investigate the effects of exercise on vascular function in women with endothelial dysfunction, or risk factors for preeclampsia.