Effects of High Altitude on AMPK Activation

Официальное название

Effects of High Altitude on 5' Adenosine Monophosphate-activated Protein Kinase (AMPK) Activation and Peroxisome Proliferator-activated Receptor Gamma (PPARγ) Regulation

Обзор

Pregnancy elicits adaptive changes in uteroplacental blood flow, which are altered at high altitude and may contribute to the observed 3-fold increase in intrauterine growth restriction (IUGR) and preeclampsia (PreE). The investigators propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA). If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders.

Подробное описание

The Investigators will determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries. This will be novel information regarding pregnancy at altitude and of significance not just for women and families in Colorado, but also at high-altitude locations throughout the world. If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders.

The Investigators will also determine whether the chronic hypoxia of high altitude alters DNA methylation patterns and expression of key genes involved in metabolic homeostasis in maternal, placental and fetal cells and, in turn, the relationship of these changes to fetal growth and maternal well-being.

Вмешательства

• Процедура Collection of myometrial, cord blood, and placental tissue samples
  We propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA).

Первичные конечные точки

• Changes in Myometrial artery dimensions [Срок оценки: Up to 1 year]

Критерии участия

Критерии включения

• Women scheduled for cesarean delivery at University of Colorado Hospital (Denver, 1600 m) and St. Anthony's Summit Medical Center (Summit County, 3000 m)
• Cesarean delivery at a prescheduled time without any labor, typically at 39 weeks gestation

Критерии исключения

• Women will be excluded if there are co-existing medical diagnoses that are known to affect vascular parameters (i.e., diabetes mellitus, gestational diabetes, any hypertensive disorder of pregnancy, or a current smoker).
• Women with multiple gestations and preterm deliveries will also be excluded.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• University of Colorado Denver Anschutz Medical Campus — Aurora

Публикации

• Osol G, Moore LG. Maternal uterine vascular remodeling during pregnancy. Microcirculation. 2014 Jan;21(1):38-47. doi: 10.1111/micc.12080. PMID 23941526
• Zamudio S, Palmer SK, Droma T, Stamm E, Coffin C, Moore LG. Effect of altitude on uterine artery blood flow during normal pregnancy. J Appl Physiol (1985). 1995 Jul;79(1):7-14. doi: 10.1152/jappl.1995.79.1.7. PMID 7559250
• Krampl ER, Espinoza-Dorado J, Lees CC, Moscoso G, Bland JM, Campbell S. Maternal uterine artery Doppler studies at high altitude and sea level. Ultrasound Obstet Gynecol. 2001 Dec;18(6):578-82. doi: 10.1046/j.0960-7692.2001.00579.x. PMID 11844192
• Julian CG, Galan HL, Wilson MJ, Desilva W, Cioffi-Ragan D, Schwartz J, Moore LG. Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude. Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R906-15. doi: 10.1152/ajpregu.00164.2008. Epub 2008 Jun 25. PMID 18579652
• Palmer SK, Moore LG, Young D, Cregger B, Berman JC, Zamudio S. Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado. Am J Obstet Gynecol. 1999 May;180(5):1161-8. doi: 10.1016/s0002-9378(99)70611-3. PMID 10329872
• Moore LG, Hershey DW, Jahnigen D, Bowes W Jr. The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude. Am J Obstet Gynecol. 1982 Oct 15;144(4):423-9. doi: 10.1016/0002-9378(82)90248-4. PMID 7124861
• Jensen GM, Moore LG. The effect of high altitude and other risk factors on birthweight: independent or interactive effects? Am J Public Health. 1997 Jun;87(6):1003-7. doi: 10.2105/ajph.87.6.1003. PMID 9224184
• Keyes LE, Armaza JF, Niermeyer S, Vargas E, Young DA, Moore LG. Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia. Pediatr Res. 2003 Jul;54(1):20-5. doi: 10.1203/01.PDR.0000069846.64389.DC. Epub 2003 Apr 16. PMID 12700368

Идентификаторы

NCT: NCT02391519 · 14-2178

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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