Browsing by Autor "Megan J. Wilson"

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Andean and Tibetan patterns of adaptation to high altitude
(Wiley, 2013) Abigail W. Bigham; Megan J. Wilson; Colleen G. Julian; Melisa Kiyamu; Enrique Vargas; Fabiola Lèon‐Velarde; Maria C. Rivera; Carmelo Rodriquez; Vaughn A. Browne; Esteban J. Parra
These results contribute to our understanding of the unique set of adaptations developed in different highland groups to the hypoxia of high altitude. Overall, the results provide key insights into the patterns of genetic adaptation to high altitude in Andean and Tibetan populations.
Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth
(American Physiological Society, 2009) Colleen G. Julian; Megan J. Wilson; M. de la Flor; Henry Yamashiro; Wilma Téllez; Armando Rodríguez; Abigail W. Bigham; Mark D. Shriver; Carmelo Rodriguez; Enrique Vargas
The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.g., Europeans). Uterine artery (UA) blood flow is greater during pregnancy in Andeans than Europeans at high altitude; however, it is not clear whether such blood flow differences play a causal role in ancestry-associated variations in fetal growth. We tested the hypothesis that greater UA blood flow contributes to the protection of fetal growth afforded by Andean ancestry by comparing UA blood flow and fetal growth throughout pregnancy in 137 Andean or European residents of low (400 m; European n = 28, Andean n = 23) or high (3,100-4,100 m; European n = 51, Andean n = 35) altitude in Bolivia. Blood flow and fetal biometry were assessed by Doppler ultrasound, and maternal ancestry was confirmed, using a panel of 100 ancestry-informative genetic markers (AIMs). At low altitude, there were no ancestry-related differences in the pregnancy-associated rise in UA blood flow, fetal biometry, or birth weight. At high altitude, Andean infants weighed 253 g more than European infants after controlling for gestational age and other known influences. UA blood flow and O(2) delivery were twofold greater at 20 wk in Andean than European women at high altitude, and were paralleled by greater fetal size. Moreover, variation in the proportion of Indigenous American ancestry among individual women was positively associated with UA diameter, blood flow, O(2) delivery, and fetal head circumference. We concluded that greater UA blood flow protects against hypoxia-associated reductions in fetal growth, consistent with the hypothesis that genetic factors enabled Andeans to achieve a greater pregnancy-associated rise in UA blood flow and O(2) delivery than European women at high altitude.
Do Anti-angiogenic or Angiogenic Factors Contribute to the Protection of Birth Weight at High Altitude Afforded by Andean Ancestry?
(Springer Nature, 2010) R. Daniela Dávila; Colleen G. Julian; Megan J. Wilson; Vaughn A. Browne; Carmelo Rodriguez; Abigail W. Bigham; Mark D. Shriver; Enrique Vargas; Lorna G. Moore
Do Cytokines Contribute to the Andean-Associated Protection From Reduced Fetal Growth at High Altitude?
(Springer Nature, 2010) R. Daniela Dávila; Colleen G. Julian; Megan J. Wilson; Vaughn A. Browne; Carmelo Rodriguez; Abigail W. Bigham; Mark D. Shriver; Enrique Vargas; Lorna G. Moore
Greater uterine artery blood flow during pregnancy in multigenerational (Andean) than shorter-term (European) high-altitude residents
(American Physiological Society, 2007) Megan J. Wilson; M. de la Flor; Marco Antonio Paco Vargas; Colleen G. Julian; Wilma Téllez; Armando Rodríguez; Abigail W. Bigham; J. Fernando Armaza; Susan Niermeyer; Mark D. Shriver
Multigenerational (Andean) compared with shorter-term (European) high-altitude residents exhibit less hypoxia-associated reductions in birth weight. Because differences in arterial O(2) content are not responsible, we asked whether greater pregnancy-associated increases in uterine artery (UA) blood flow and O(2) delivery were involved. Serial studies were conducted in 42 Andean and 26 European residents of La Paz, Bolivia (3600 m) at weeks 20, 30, 36 of pregnancy and 4 mo postpartum using Doppler ultrasound. There were no differences postpartum but Andean vs. European women had greater UA diameter (0.65 +/- 0.01 vs. 0.56 +/- 0.01 cm), cross-sectional area (33.1 +/- 0.97 vs. 24.7 +/- 1.18 mm(2)), and blood flow at week 36 (743 +/- 87 vs. 474 +/- 36 ml/min) (all P < 0.05) and thus 1.6-fold greater uteroplacental O(2) delivery near term (126.82 +/- 18.47 vs. 80.33 +/- 8.69 ml O(2).ml blood(-1).min(-1), P < 0.05). Andeans had greater common iliac (CI) flow and lower external iliac relative to CI flow (0.52 +/- 0.11 vs. 0.95 +/- 0.14, P < 0.05) than Europeans at week 36. After adjusting for gestational age, maternal height, and parity, Andean babies weighed 209 g more than the Europeans. Greater UA cross-sectional area at week 30 related positively to birth weight in Andeans (r = +0.39) but negatively in Europeans (r = -0.37) (both P < 0.01). We concluded that a greater pregnancy-associated increase in UA diameter raised UA blood flow and uteroplacental O(2) delivery in the Andeans and contributed to their ability to maintain normal fetal growth under conditions of high-altitude hypoxia. These data implicate the involvement of genetic factors in protecting multigenerational populations from hypoxia-associated reductions in fetal growth, but future studies are required for confirmation and identification of the specific genes involved.
High-altitude ancestry protects against hypoxia-associated reductions in fetal growth
(BMJ, 2007) Colleen G. Julian; Enrique Vargas; J. Fernando Armaza; Megan J. Wilson; Susan Niermeyer; Lorna G. Moore
Andean relative to European ancestry protects against altitude-associated reductions in fetal growth. The intermediate protection seen in the admixed (Mestizo) group is consistent with the influence of genetic or other Andean-specific protective characteristics.
High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude
(American Physiological Society, 2011) Vaughn A. Browne; Lilian Toledo‐Jaldin; R. Daniela Dávila; Luis P. Lopez; Henry Yamashiro; Darleen Cioffi‐Ragan; Colleen G. Julian; Megan J. Wilson; Abigail W. Bigham; Mark D. Shriver
The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (Q(UA)). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600-4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ~0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. Q(UA) was lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left Q(UA) was consistently greater than right in NORM, but the pattern reversed in PE. Although Q(CI) and Q(EI) were higher in PE and GH than NORM, the fraction of Q(CI) distributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced Q(UA) (R(2) = 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited Q(UA) and restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of Q(UA) and pelvic blood flow in early- vs. late-onset PE in high-altitude residents.
Lowland origin women raised at high altitude are not protected against lower uteroplacental O2 delivery during pregnancy or reduced birth weight
(Wiley, 2011) Colleen G. Julian; Jennifer L. Hageman; Megan J. Wilson; Enrique Vargas; Lorna G. Moore
Lifelong compared with newcomer high-altitude residents have lower uteroplacental O(2) delivery and similar infant birth weights, suggesting that developmental factors are likely not responsible for the protective effect of highland ancestry.
Maternal Adaptation to High-altitude Pregnancy: An Experiment of Nature—A Review
(Elsevier BV, 2004) Lorna G. Moore; Mark D. Shriver; Lynne Bemis; B. Hickler; Megan J. Wilson; Tom D. Brutsaert; Esteban J. Parra; Enrique Vargas
MaternalPRKAA1andEDNRAgenotypes are associated with birth weight, andPRKAA1with uterine artery diameter and metabolic homeostasis at high altitude
(American Physical Society, 2014) Abigail W. Bigham; Colleen G. Julian; Megan J. Wilson; Enrique Vargas; Vaughn A. Browne; Mark D. Shriver; Lorna G. Moore
Low birth weight and intrauterine growth restriction (IUGR) increase the risk of mortality and morbidity during the perinatal period as well as in adulthood. Environmental and genetic factors contribute to IUGR, but the influence of maternal genetic variation on birth weight is largely unknown. We implemented a gene-by-environment study wherein we utilized the growth restrictive effects of high altitude. Multigenerational high-altitude residents (Andeans) are protected from altitude-associated IUGR compared with recent migrants (Europeans). Using a combined cohort of low- and high-altitude European and Andean women, we tested 63 single nucleotide polymorphisms (SNPs) from 16 natural selection-nominated candidate gene regions for associations with infant birth weight. We identified significant SNP associations with birth weight near coding regions for two genes involved in oxygen sensing and vascular control, PRKAA1 and EDNRA, respectively. Next, we identified a significant association for the PRKAA1 SNP with an intermediate phenotype, uterine artery diameter, which has been shown to be related to Andean protection from altitude-associated reductions in fetal growth. To explore potential functional relationships for the effect of maternal SNP genotype on birth weight, we evaluated the relationship between maternal PRKAA1 SNP genotype and gene expression patterns in general and, in particular, of key pathways involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of IUGR. Our observations suggest that maternal genetic variation within genes that regulate oxygen sensing, metabolic homeostasis, and vascular control influence fetal growth and birth weight outcomes and hence Andean adaptation to high altitude.
PlGF is greater and sFLT‐1 lower in multigenerational vs. shorter‐term pregnant residents of high altitude
(Wiley, 2008) R. Daniela Dávila; Colleen G. Julian; Vaughn A. Browne; Megan J. Wilson; Jennifer L. Hageman; Henry Yamashiro; Armando Rodríguez; Carmelo Rodriguez; Enrique Vargas; Lorna G. Moore
INTRODUCTION. An imbalance between angiogenic and anti‐angiogenic factors likely plays an etiological role in fetal growth restriction. Since multigenerational high‐altitude (HA) Andean (AND) vs. shorter‐term, European (EUR) ancestry protects against fetal growth restriction at HA, we hypothesized that the angiogenic factor PlGF was elevated and the anti‐angiogenic factor sFlt‐1 reduced. MATERIALS AND METHODS. Pregnant women residing at low (400 m; AND n=36, EUR n=39) or high (3600m; AND n=46, EUR n=33) altitude in Bolivia were studied at 20 and 36 wk of pregnancy and 4 mo postpartum. Plasma sFlt1 and PlGF levels were determined by ELISA and data analyzed by ANOVA. RESULTS. Pregnancy increased PlGF and sFlt‐1 in EUR and AND women (p<0.001). PlGF increased in AND women at HA in early pregnancy and declined at 36 wk compared EUR values (interaction between pregnancy, altitude and ancestry, p<0.05). At HA, sFlt‐1 was greater in EUR than AND women at 20 and 36 wk (p<0.001). The sFlt‐1/PlGF ratio rose from 20 wk to 36 wk in EUR women at both altitudes and in HA AND women but not in the LA AND, and tended to be lower in AND vs. EUR women near term (p<0.10). CONCLUSIONS. Lower sFLT‐1 and higher PlGF levels may help protect multigenerational AND compared with shorter‐term EUR HA‐residents from fetal growth restriction. (NIH HL079647 and HL 14985)
Potential role for elevated maternal enzymatic antioxidant status in Andean protection against altitude-associated SGA
(Informa, 2011) Colleen G. Julian; Enrique Vargas; Vaughn A. Browne; Megan J. Wilson; Abigail W. Bigham; Carmelo Rodriguez; Joe M. McCord; Lorna G. Moore
Oxidative stress has been implicated in the uteroplacental ischemia characteristic of preeclampsia and small-for-gestational-age (SGA) birth, both of which are more common at high (>2500 m) vs low altitude. Since Andeans are protected relative to Europeans from the altitude-associated rise in SGA, we asked whether alterations in maternal antioxidant status or oxidative stress contributed to their protection. Enzymatic antioxidant (erythrocyte catalase and superoxide dismutase [SOD]) activity and a plasma marker of lipid peroxidation (8-iso-PGF2α) were measured during pregnancy and in the non-pregnant state in Andean or European residents of low (400 m) or high altitude (3600-4100 m). Pregnancy and altitude increased catalase and/or SOD activity to a greater extent in Andeans than Europeans. 8-iso-PGF2α levels were independent of altitude and pregnancy. SOD was lower in mothers of SGA infants at weeks 20 and 36. Our findings are consistent with the possibility that elevated enzymatic antioxidant activity contributes to Andean protection against altitude-associated SGA.
Role of cytokines in altitude-associated preeclampsia
(Elsevier BV, 2011) R. Daniela Dávila; Colleen G. Julian; Vaughn A. Browne; Lillian Toledo-Jaldin; Megan J. Wilson; Armando Rodríguez; Enrique Vargas; Lorna G. Moore
The role of antioxidant & oxidative status in the protection against altitude‐associated reductions in uterine artery (UA) blood flow & fetal growth afforded by Andean ancestry
(Wiley, 2008) Colleen G. Julian; Enrique Vargas; Joe M. McCord; Jennifer L. Hageman; R. Daniela Dávila; Henry Yamashiro; Megan J. Wilson; Carmelo Rodriguez; Armando Rodríguez; Vaughn A. Browne
Objective: To determine the role of antioxidant & oxidative status in the protection of uterine artery blood flow (UAVF) & fetal growth at high altitude in Andean populations. Methods: Erythrocyte catalase (CAT) & superoxide dismutase (SOD), plasma isoprostanes (8‐ISO‐PGF‐2α) & UA VF were measured at 20 & 36w of pregnancy & and in the non‐pregnant state in Andean (AND) & European (EUR) women at low (LA, 416m) or high (HA, 3600m) altitude. CAT, SOD & 8‐iso‐PGF‐2α were assessed by spectrometry, UA VF by Doppler ultrasound & birth weight (BW) by medical records review. Data was analyzed by t‐tests, 1‐ & 2‐way ANOVA. Results: At LA, ancestry had no effect on CAT or SOD. AND had higher CAT (20 & 36w p<0.05) & SOD activity (36w p<0.05) than EUR at HA. At HA, UA diameter and UA VF were greater in AND than EUR. Altitude decreased BW in AND (p<0.05) and EUR (p<0.01), and at HA EUR ancestry reduced BW (β= − 0.238 p<0.05). Small‐for‐gestational age (SGA) infants occurred 2‐times more frequently at HA than LA in EUR. SOD was lower at 20w in SGA at both altitues, or HA alone (all p<0.05). In EUR, CAT tended to be lower at 20w in SGA. 8‐ISO‐PGF2α reduced UA diam (p<0.05) & UA VF (p<0.01) in all women. Conclusion: Elevated endogenous antioxidant activity may contribute to the protection against altitude‐associated reductions in UA blood flow & fetal growth afforded by Andean ancestry. NIH HL079647 ,AHA 0610129Z & NSF BCS‐064719.