Browsing by Autor "Carmelo Rodriguez"

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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
Inhibition of peroxisome proliferator‐activated receptor γ: a potential link between chronic maternal hypoxia and impaired fetal growth
(Wiley, 2013) Colleen G. Julian; Ivana V. Yang; Vaughn A. Browne; Enrique Vargas; Carmelo Rodriguez; Brent S. Pedersen; Lorna G. Moore; David A. Schwartz
Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxia-related effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-level residents in the nonpregnant state or during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes apparent between 25 and 29 wk of gestation and continues until delivery. Our sampling strategy was designed to capture changes occurring before (20 wk) and during (36 wk) the time frame of slowed fetal growth. PBMC gene expression profiles were generated using human gene expression microarrays and compared between altitudes. Biological pathways were identified using pathway analysis. Modest transcriptional differences were observed between altitudes in the nonpregnant state. Of the genes that were differentially expressed at high altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36 wk: 985 probes mapped to 700 genes), several are of pathological relevance for fetal growth restriction. In particular, transcriptional changes were consistent with the negative regulation of peroxisome proliferator-activated receptor γ (PPARγ) at high altitude; such effects were accompanied by reduced birth weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level. Our findings indicate that chronic exposure to hypoxia during pregnancy alters maternal gene expression patterns in general and, in particular, expression of key genes involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of fetal growth restriction.
Maternal oxygen delivery is not related to altitude‐ and ancestry‐associated differences in human fetal growth
(Wiley, 2007) Stacy Zamudio; Lucrecia Postigo; Nicholas P. Illsley; Carmelo Rodriguez; Gladys Heredia; Michael Brimacombe; Lourdes Echalar; Tatiana Torricos; Wilma Téllez; Iván Maldonado
Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O(2) delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O(2) delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n=180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphism. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P<0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O(2) delivery regardless of ancestry. But the hypothesis was rejected as O(2) delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O(2) delivery, regardless of altitude (P<0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P<0.01), but admixture was not related to any of the O(2) transport variables. Genetically mediated differences in maternal O(2) delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O(2) and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O(2) delivery in these pregnancies was 99 +/- 3 ml min(-1), approximately 5-fold greater than near-term fetal O(2) consumption. Deficits in maternal O(2) transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth.
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.
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.