Do Anti-angiogenic or Angiogenic Factors Contribute to the Protection of Birth Weight at High Altitude Afforded by Andean Ancestry?

Dávila, R. Daniela; Julian, Colleen G.; Wilson, Megan J.; Browne, Vaughn A.; Rodriguez, Carmelo; Bigham, Abigail W.; Shriver, Mark D.; Vargas, Enrique; Moore, Lorna G.

doi:10.1177/1933719110372418

Cited by 23 publications

(24 citation statements)

References 46 publications

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“…Physiologically, the short variant of sFlt-1 has been associated with increased sFlt-1 expression and low birth weight in first-time mothers (Muehlenbachs et al , 2008), while low levels of sFlt-1 were protective against low birth weight (Davila et al , 2010). Also, pathological elevations of sFlt-1 have been well characterized and highly implicated in pre-eclampsia (McMahon et al , 2014; Levine et al , 2004).…”

Section: Discussionmentioning

confidence: 99%

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Lizano

Keshavan

Tandon

et al. 2016

Schizophrenia Research

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Schizophrenia (SZ) is a heterogeneous disorder that presents in adolescence, persists into adulthood, and has many clinical features. Recent evidence suggests that abnormalities in inflammatory, neurotrophic, and angiogenic processes may play a role in the etiology of SZ. The identification of molecular biomarkers early in the course of disease is crucial to transforming diagnostic and therapeutic avenues. We investigated 14 molecular analytes focusing on inflammatory, neurotrophic and angiogenic pathways from the plasma of antipsychotic-naïve familial high risk for SZ (FHR; n=35) and first-episode psychosis (FEP; n=45) subjects, in comparison to healthy controls (HC, n=39). We identified distinct alterations in molecular signatures in young relatives at FHR for SZ prior to psychosis onset and FEP subjects. Firstly, the expression of soluble fms-like tyrosine kinase (sFlt-1), an anti-angiogenic factor that binds vascular endothelial growth factor (VEGF), was significantly increased in the FHR group compared to HC, but not in FEP. Secondly, interferon gamma (IFNγ) was significantly reduced in the FEP group compared to HC. Thirdly, network analysis revealed a positive correlation between sFlt-1 and VEGF, suggesting an activation of the angiogenic cascade in the FHR group, which persists in FEP. Our results indicate an angiogenesis and immunological dysfunction early in the course of disease, shifting the balance towards anti-angiogenesis and inflammation.

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Section: Discussionmentioning

confidence: 99%

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Lizano

Keshavan

Tandon

et al. 2016

Schizophrenia Research

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“…Our recent Bolivian investigations support the likelihood that a more favorable balance of angiogenic to anti-angiogenic factors plays a role in the Andeans’ larger UA diameters. Specifically, Andean compared with European women at high altitude had lower ratios of the anti-angiogenic substance sFlt-1 relative to the pro-angiogenic PlGF, which was due entirely to lower sFlt-1 levels (Davila et al, 2010). …”

Section: 0 Maternal Factors Influencing Fetal Growthmentioning

confidence: 99%

Humans at high altitude: Hypoxia and fetal growth

Moore

Charles

Julian

2011

Respiratory Physiology & Neurobiology

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227

140

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High-altitude studies offer insight into the evolutionary processes and physiological mechanisms affecting the early phases of the human lifespan. Chronic hypoxia slows fetal growth and reduces the pregnancy-associated rise in uterine artery (UA) blood flow. Multigenerational vs. shorter-term high-altitude residents are protected from the altitude-associated reductions in UA flow and fetal growth. Presently unknown is whether this fetal-growth protection is due to the greater delivery or metabolism of oxygen, glucose or other substrates or to other considerations such as mechanical factors protecting fragile fetal villi, the creation of a reserve protecting against ischemia/reperfusion injury, or improved placental O2 transfer as the result of narrowing the A-V O2 difference and raising uterine PvO2. Placental growth and development appear to be normal or modified at high altitude in ways likely to benefit diffusion. Much remains to be learned concerning the effects of chronic hypoxia on embryonic development. Further research is required for identifying the fetoplacental and maternal mechanisms responsible for transforming the maternal vasculature and regulating UA blood flow and fetal growth. Genomic as well as epigenetic studies are opening new avenues of investigation that can yield insights into the basic pathways and evolutionary processes involved.

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“…Uterine artery blood fl ow was twofold higher in Andean than European women at high altitude; these differences corresponded to greater fetal size among Andeans and a birth weight differential of 253 g after controlling for gestational age, maternal height, and parity. Study of angiogenic factors during pregnancy has shown that Andeans compared to Europeans at high altitude had lower sFlt-1 and sFlt-1/PlGF ratio during pregnancy, and these values corresponded to higher uterine artery blood fl ow and birth weight [ 58 ]. Among women residing at 1,600 and 3,100 m in Colorado, changes in uterine artery fl ow and the ratio of endothelin-1 to nitric oxide (ET-1/NOx) preceded changes in fetal growth and correlated with ultimate birth weight reduction [ 59 ].…”

Section: Maternal Oxygen and Nutrient Transport During Pregnancymentioning

confidence: 97%

Reproduction and Growth

Niermeyer

2013

High Altitude

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Reproduction and development during infancy and childhood present critical, vulnerable periods in the individual lifecycle and the health of a population. For humans living permanently at high altitude, the environment they inhabit adds risks for maternal and child health and survival. In addition to hypoxia, many high-altitude regions impose other constraints on the circumstances necessary for optimal fetal development and infant/child survival. These include impoverished living conditions, social inequalities, physically demanding livelihoods, nutritional defi ciencies, and infectious diseases. Such determinants infl uence fertility, fetal loss and growth, neonatal survival, and child development. Populations resident at high altitude for millennia, for example the Tibetans in the Himalaya and the Aymara and Quechua of South America, attest to possibility of not only surviving but also thriving, Hypoxia, as well as other environmental and social factors, shapes reproduction and fetal/infant growth at high altitude. Although fertility and early fetal loss differ little from patterns observed at lower altitude, placental development does differ and the medical complications of pre-eclampsia and post-partum hemorrhage pose greater risks at altitude. Reduction in birth weight with increasing altitude of gestation occurs across high-altitude regions, resulting in an increased proportion of lowbirth-weight infants (<2,500 g). However, the magnitude of reduction in fetal growth varies among population groups, depending on maternal ventilation, plasma volume expansion, blood fl ow to the uteroplacental circulation, and nutrient transport. Neonatal, infant, and child mortality are increased at high altitude. Respiratory problems account for the majority of neonatal and infant deaths. Exposure to hypoxia during the fetal and neonatal periods may have consequences that extend into adult life and span generations.

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Do Anti-angiogenic or Angiogenic Factors Contribute to the Protection of Birth Weight at High Altitude Afforded by Andean Ancestry?

Cited by 23 publications

References 46 publications

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Humans at high altitude: Hypoxia and fetal growth

Reproduction and Growth

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