Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-26T17:12:17.812Z Has data issue: false hasContentIssue false
  • English
  • Français

The newborn sheep translational model for pulmonary arterial hypertension of the neonate at high altitude

Published online by Cambridge University Press:  24 July 2020

Alejandro Gonzaléz-Candia Open the ORCID record for Alejandro Gonzaléz-Candia [Opens in a new window] ,
Alejandro A. Candia ,
Germán Ebensperger ,
Roberto V. Reyes ,
Aníbal J. Llanos  and
Emilio A. Herrera
Alejandro Gonzaléz-Candia
Affiliation:
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
Alejandro A. Candia
Affiliation:
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile Department for the Woman and Newborn Health Promotion, Universidad de Chile, Santiago, Chile
Germán Ebensperger
Affiliation:
Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
Roberto V. Reyes
Affiliation:
Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile
Aníbal J. Llanos
Affiliation:
Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile
Emilio A. Herrera*
Affiliation:
Laboratory of Vascular Function and Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile
*
Address for correspondence: Emilio A. Herrera, Laboratorio de Función y Reactividad Vascular, Programa de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Av. Salvador 486, Providencia 7500922, Santiago, Chile. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Chronic hypoxia during gestation induces greater occurrence of perinatal complications such as intrauterine growth restriction, fetal hypoxia, newborn asphyxia, and respiratory distress, among others. This condition may also cause a failure in the transition of the fetal to neonatal circulation, inducing pulmonary arterial hypertension of the neonate (PAHN), a syndrome that involves pulmonary vascular dysfunction, increased vasoconstrictor tone and pathological remodeling. As this syndrome has a relatively low prevalence in lowlands (~7 per 1000 live births) and very little is known about its prevalence and clinical evolution in highlands (above 2500 meters), our understanding is very limited. Therefore, studies on appropriate animal models have been crucial to comprehend the mechanisms underlying this pathology. Considering the strengths and weaknesses of any animal model of human disease is fundamental to achieve an effective and meaningful translation to clinical practice. The sheep model has been used to study the normal and abnormal cardiovascular development of the fetus and the neonate for almost a century. The aim of this review is to highlight the advances in our knowledge on the programming of cardiopulmonary function with the use of high-altitude newborn sheep as a translational model of PAHN.

Keywords

Hypoxiahypobariaepigeneticshigh altitudeDOHaD
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 5 , October 2020 , pp. 452 - 463
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abman, SH.Recent advances in the pathogenesis and treatment of persistent pulmonary hypertension of the newborn. Neonatology. 2007; 91, 283–290.CrossRefGoogle ScholarPubMed
Herrera, EA, Pulgar, VM, Riquelme, RA, et al.High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R2234–R2240.CrossRefGoogle ScholarPubMed
Rabinovitch, M.Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 2008; 118, 2372–2379.CrossRefGoogle ScholarPubMed
Gao, Y, Raj, U.Hypoxic pulmonary hypertension of the newborn. Compr Physiol. 2011; 1(1), 61–79.Google ScholarPubMed
Morrison, JL, Berry, MJ, Botting, KJ, et al.Improving pregnancy outcomes in humans through studies in sheep. Am J Physiol Regul Integr Comp Physiol. 2018; 1–315(6), R1123–R1153.CrossRefGoogle Scholar
Walsh-Sukys, MC, Tyson, JE, Wright, LL, et al.Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics. 2000; 105, 14e20.CrossRefGoogle ScholarPubMed
Keyes, LE, Armaza, JF, Niermeyer, S, et al.Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia. Pediat Res. 2003; 54, 20–22.CrossRefGoogle ScholarPubMed
Li, JJ, Liu, Y, Xie, SY, et al.Newborn screening for congenital heart disease using echocardiography and follow-up at high altitude in China. Int J Cardiol. 2019; 274, 106–112.CrossRefGoogle ScholarPubMed
Moore, LG, Shriver, M, Bemis, L, et al.Maternal adaptation to high-altitude pregnancy: an experiment of nature–a review. Placenta. 2004; 25(Suppl A), S60–S71.CrossRefGoogle ScholarPubMed
Ducsay, CA, Goyal, R, Pearce, WJ, et al.Gestational hypoxia and developmental plasticity. Physiol Rev. 2018; 98(3), 1241–1334.CrossRefGoogle ScholarPubMed
Li, Y, Gonzalez, P, Zhang, L.Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions. Prog Neurobiol. 2012; 98(2), 145–165.CrossRefGoogle ScholarPubMed
Alexander, BT, Dasinger, JH, Intapad, S.Fetal programming and cardiovascular pathology. Compr Physiol. 2012; 5, 997–1025.Google Scholar
Kubota, T, Miyake, K, Hariya, N, Mochizuki, K.Understanding the epigenetics of neurodevelopmental disorders and DOHaD. J Dev Orig Health Dis. 2015; 6, 1–9.CrossRefGoogle ScholarPubMed
Barker, DJ, Osmond, C.Death rates from stroke in England and Wales predicted from past maternal mortality. BMJ. 1987; 295, 83–86.CrossRefGoogle ScholarPubMed
Keating, ST, El-Osta, A.Epigenetics and metabolism. Circ Res. 2015; 116, 715–736.CrossRefGoogle ScholarPubMed
Goyal, D, Limesand, SW, Goyal, R.Epigenetic responses and the developmental origins of health and disease. J Endocrinol. 2019; 242(1), 105–119.CrossRefGoogle ScholarPubMed
Papamatheakis, DG, Blood, AB, Kim, JH, Wilson, SM.Antenatal hypoxia and pulmonary vascular function and remodeling. Curr Vasc Pharmacol. 2013; 11(5), 616–640.CrossRefGoogle ScholarPubMed
Parrau, D, Ebensperger, G, Herrera, EA, et al.Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs. Am J Physiol Lung Cell Mol Physiol. 2013; 304(8), L540–L548.CrossRefGoogle ScholarPubMed
Llanos, AJ, Ebensperger, G, Herrera, EA, et al.Fetal and postnatal pulmonary circulation in the Alto Andino. Placenta. 2011; 32–32, S100–S103.CrossRefGoogle Scholar
Castillo-Galán, S, Quezada, S, Moraga, FA, et al.2-aminoethyldiphenylborinate modifies the pulmonary circulation in pulmonary hypertensive newborn lambs with partial gestation at high altitude. Am J Physiol Lung Cell Mol Physiol. 2016; 311(4), L788–L799.CrossRefGoogle ScholarPubMed
Herrera, EA, Rojas, RT, Krause, BJ, et al.Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the Andean altiplano. J Physiol. 2016; 5, 1231–1245.CrossRefGoogle Scholar
Lopez, NC, Ebensperger, G, Herrera, EA, et al.Role of the RhoA/ROCK pathway in high-altitude associated neonatal pulmonary hypertension in lambs. Am J Physiol Regul Integr Comp Physiol. 2016; 310, R1053–R1063.CrossRefGoogle ScholarPubMed
Gonzaléz-Candia, A, Candia, AA, Figueroa, EG, et al.Melatonin long lasting beneficial effects on pulmonary vascular reactivity and redox balance in chronic hypoxic ovine neonates. J Pineal Res. 2019; 68(4), e12613.Google ScholarPubMed
Ziino, AJ, Ivanovska, J, Belcastro, R, et al.Effects of rho-kinase inhibition on pulmonary hypertension, lung growth, and structure in neonatal rats chronically exposed to hypoxia. Pediatr Res. 2010; 67(2), 177–182.CrossRefGoogle ScholarPubMed
Bierer, R, Nitta, CH, Friedman, JK, et al.NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. Am J Physiol Lung Cell Mol Physiol. 2011; 301(6), L872–L880.CrossRefGoogle ScholarPubMed
Hirenallur, SD, Haworth, ST, Leming, JT, et al.Upregulation of vascular calcium channels in neonatal piglets with hypoxia-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2008; 295(5), L915–L924.CrossRefGoogle Scholar
Murphy, JD, Aronovitz, MJ, Reid, LM.Effects of chronic in utero hypoxia on the pulmonary vasculature of the newborn guinea pig. Pediatr Res. 1986; 20(4), 292–295.CrossRefGoogle ScholarPubMed
Herrera, EA, Alegría, R, Farias, M, et al.Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs. J Physiol. 2016; 594(6), 1553–1561.CrossRefGoogle Scholar
Giussani, DA, Riquelme, RA, Sanhueza, EM, Hanson, MA, Blanco, CE, Llanos, AJ.Adrenergic and vasopressinergic contributions to the cardiovascular response to acute hypoxaemia in the llama fetus. J Physiol. 1999; 515 (Pt 1)(Pt 1), 233–241.CrossRefGoogle ScholarPubMed
Llanos, AJ, Riquelme, RA, Sanhueza, EM, et al.The fetal llama versus the fetal sheep: different strategies to withstand hypoxia. High Alt Med Biol. 2003; 4(2), 193–202.CrossRefGoogle ScholarPubMed
Herrera, EA, Ebensperger, G, Krause, BJ, et al.Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep. Pediatr Res. 2008; 63, 169e75.CrossRefGoogle ScholarPubMed
Reyes, RV, Díaz, M, Ebensperger, G, et al.The role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn llamas. J Physiol. 2018; 596(23), 5907–5923.CrossRefGoogle ScholarPubMed
Hillman, NH, Kallapur, SG, Jobe, AH.Physiology of transition from intrauterine to extrauterine life. Clin Perinatol. 2012; 39(4), 769–783.CrossRefGoogle ScholarPubMed
Herrera, EA, Krause, BJ, Ebensperger, G, et al.The placental pursuit for anadequate oxidant balance between the mother and the fetus. Front Pharmacol. 2014; 5, 149.CrossRefGoogle ScholarPubMed
Torres, F, González-Candia, A, Montt, C, et al.Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep. J Pineal Res. 2015; 58(3), 362–373.CrossRefGoogle ScholarPubMed
Cohn, HE, Sacks, EJ, Heymann, MA, Rudolph, AM.Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol. 1974; 120(6), 817–824.CrossRefGoogle ScholarPubMed
Peréz, R, Espinoza, M, Riquelme, R, Parer, JT, Llanos, AJ.Arginine vasopressin mediates cardiovascular responses to hypoxemia in fetal sheep. Am J Physiol. 1989; 256(5 Pt 2), R1011–R1018.Google ScholarPubMed
Rudolph, AM.Circulatory changes during gestational development of the sheep and human fetus. Pediatr Res. 2018; 84(3), 348–351.CrossRefGoogle ScholarPubMed
Llanos, AJ, Green, JR, Creasy, RK, Rudolph, AM.Increased heart rate response to parasympathetic and beta adrenergic blockade in growth-retarded fetal lambs. Am J Obstet Gynecol. 1980; 136(6), 808–813.CrossRefGoogle ScholarPubMed
Allison, BJ, Brain, KL, Niu, Y, et al.Fetal in vivo continuous cardiovascular function during chronic hypoxia. J Physiol. 2016; 594(5), 1247–1264.CrossRefGoogle ScholarPubMed
Shaw, CJ, Allison, BJ, Itani, N, et al.Altered autonomic control of heart rate variability in the chronically hypoxic fetus. J Physiol. 2018; 596(23), 6105–6119.CrossRefGoogle ScholarPubMed
Edea, Z, Dadi, H, Dessie, T, Kim, KS.Genomic signatures of high-altitude adaptation in Ethiopian sheep populations. Genes Genomics. 2019; 41(8), 973–981.CrossRefGoogle ScholarPubMed
Ma, Y, Ma, S, Chang, L, et al.Gut microbiota adaptation to high altitude in indigenous animals. Biochem Biophys Res Commun. 2019; 526(1), 120–126.CrossRefGoogle Scholar
Gorkhali, NA, Dong, K, Yang, M, et al.Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas. Sci Rep. 2016; 6, 29963.CrossRefGoogle ScholarPubMed
Parraguez, VH, Mamani, S, Cofré, E, et al.Disturbances in maternal steroidogenesis and appearance of intrauterine growth retardation at high-altitude environments are established from early pregnancy. Effects of treatment with antioxidant vitamins. PLoS One. 2015; 10(11), e0140902.CrossRefGoogle ScholarPubMed
Wei, C, Wang, H, Liu, G, et al.Genome-wide analysis reveals adaptation to high altitudes in Tibetan sheep. Sci Rep. 2016; 6, 26770.CrossRefGoogle ScholarPubMed
Moretta, D, Papamatheakis, DG, Morris, DP, et al.Long-term high-altitude hypoxia and alpha adrenoreceptor-dependent pulmonary arterial contractions in fetal and adult sheep. Front Physiol. 2019; 10, 1032.CrossRefGoogle Scholar
Hu, XQ, Dasgupta, C, Xiao, J, Yang, S, Zhang, L.Long-term high altitude hypoxia during gestation suppresses large conductance Ca2+ -activated K+ channel function in uterine arteries: a causal role for microRNA-210. J Physiol. 2018; 596(23), 5891–5906.CrossRefGoogle ScholarPubMed
Myers, DA, Ducsay, CA.Altitude, attitude and adaptation. Adv Exp Med Biol. 2014; 814, 147–157.CrossRefGoogle ScholarPubMed
Wang, B, Zhang, YB, Zhang, F, et al.On the origin of Tibetans and their genetic basis in adapting high-altitude environments. PLoS One. 2011; 6, e17002.CrossRefGoogle ScholarPubMed
Browne, VA, Julian, CG, Toledo-Jaldin, L, et al.Uterine artery blood flow, fetal hypoxia and fetal growth. Philos Trans R Soc Lond B Biol Sci. 2015; 370, 20140068.CrossRefGoogle Scholar
Giussani, DA, Phillips, PS, Anstee, S, Barker, DJ.Effects of altitude versus economic status on birth weight and body shape at birth. Pediatr Res. 2011; 49, 490–494.CrossRefGoogle Scholar
Giussani, DA, Davidge, ST.Developmental programming of cardiovascular disease by prenatal hypoxia. J Dev Orig Health Dis. 2013; 4, 328–337.CrossRefGoogle ScholarPubMed
Parraguez, VC, Atlagich, M, Díaz, R, et al.Effect of hypobaric hypoxia on lamb intrauterine growth: comparison between high- and low altitude native ewes. Reprod Fertil Dev. 2005; 17, 497–505.CrossRefGoogle ScholarPubMed
Rueda-Clausen, CF, Stanley, JL, Thambiraj, DF, Poudel, R, Davidge, ST, Baker, PN. Effect of prenatal hypoxia in transgenic mouse models of preeclampsia and fetal growth restriction. Reprod Sci. 2014; 21, 492–502.CrossRefGoogle ScholarPubMed
Brain, KL, Allison, BJ, Niu, Y, et al.Induction of controlled hypoxic pregnancy in large mammalian species. Physiol Rep. 2015; 3, e12614.CrossRefGoogle ScholarPubMed
Thompson, LP, Pence, L, Pinkas, G, Song, H, Telugu, BP.Placental hypoxia during early pregnancy causes maternal hypertension and placental insufficiency in the hypoxic guinea pig model. Biol Reprod. 2016; 95, 128.CrossRefGoogle ScholarPubMed
Gonzalez-Candia, A, Veliz, M, Araya, C, et al.Potential adverse effects of antenatal melatonin as a treatment for intrauterine growth restriction: findings in pregnant sheep. Am J Obstet Gynecol. 2016; 215, 245.e1–7.CrossRefGoogle ScholarPubMed
Moore, LG, Niermeyer, S, Zamudio, S.Human adaptation to high altitude: regional and life-cycle perspectives. Am J Phys Anthropol. 1998; 107(Suppl 27), 25–64.3.0.CO;2-L>CrossRefGoogle Scholar
Longo, LD, Pearce, WJ.Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease. Am J Physiol Regul Integr Comp Physiol. 2005; 288(1), R16–R24.CrossRefGoogle Scholar
Lichty, JA.Neonatal mortality and prematurity in Colorado. Rocky Mt Med J. 1957; 54(3), 251–254.Google ScholarPubMed
Sobrevilla, LA, Cassinelli, MT, Carcelen, A, Malaga, JM.Human fetal and maternal oxygen tension and acid-base status during delivery at high altitude. Am J Obstet Gynecol. 1971; 111(8), 1111–1118.CrossRefGoogle ScholarPubMed
Ballew, C, Haas, JD.Hematologic evidence of fetal hypoxia among newborn infants at high altitude in Bolivia. Am J Obstet Gynecol. 1986; 155(1), 166–169.CrossRefGoogle ScholarPubMed
Niermeyer, S, Yang, P, Zhuang, J, Moore, LG. Arterial oxygen saturation in Tibetan and Han infants born in Lhasa, Tibet. N Engl J Med. 1995; 333(19), 1248–1252.CrossRefGoogle Scholar
Mortola, JP, Frappell, PB, Aguero, L, Armstrong, K.Birth weight and altitude: a study in Peruvian communities. J Pediatr. 2000; 136(3), 324–329.CrossRefGoogle ScholarPubMed
Penaloza, D, Arias-Stella, J.The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. Circulation. 2007; 115(9), 1132–1146.CrossRefGoogle ScholarPubMed
Niermeyer, S, Andrade Mollinedo, P, Huicho, L.Child health and living at high altitude. Arch Dis Child. 2009; 94(10), 806–811.CrossRefGoogle ScholarPubMed
Jeffery, TK, Morrell, NW.Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis. 2002; 45(3), 173–202.CrossRefGoogle ScholarPubMed
Durmowicz, AG, Stenmark, KR.Mechanisms of structural remodeling in chronic pulmonary hypertension. Pediatr Rev. 1999; 20(11), e91–e102.CrossRefGoogle ScholarPubMed
Stenmark, KR, Fagan, KA, Frid, MG.Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res. 2006; 99, 675–669.CrossRefGoogle ScholarPubMed
Beall, CM, Laskowski, D, Strohl, KP, et al.Pulmonary nitric oxide in mountain dwellers. Nature. 2001; 414, 411–412.CrossRefGoogle ScholarPubMed
Duplain, H, Sartori, C, Lepori, M, et al.Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation. Am J Respir Crit Care Med. 2000; 162, 221–224.CrossRefGoogle Scholar
Sartori, C, Rimoldi, SF, Duplain, H, et al.Developmental origins of hypoxic pulmonary hypertension and systemic vascular dysfunction: evidence from humans. Adv Exp Med Biol. 2016; 903, 17–28.CrossRefGoogle ScholarPubMed
Gamboa, R, Marticorena, E.Presión arterial pulmonar en el recién nacido en las grandes alturas [Pulmonary arterial pressure in newborn infants in high altitude]. Arch Inst Biol Andina. 1971; 4(2), 55–66.Google Scholar
Llanos, AJ, Riquelme, RA, Moraga, FA, Cabello, G, Parer, JT.Cardiovascular responses to graded degrees of hypoxemia llama fetus. Reprod Fertil Dev. 1995; 7, 549e52.CrossRefGoogle ScholarPubMed
Weir, EK, Archer, SL.The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J. 1995; 9(2), 183–189.CrossRefGoogle ScholarPubMed
Franco-Cereceda, A, Holm, P.Selective or nonselective endothelin antagonists in porcine hypoxic pulmonary hypertension. J Cardiovasc Pharmacol. 1998; 31(Suppl 1), S447–S452.CrossRefGoogle ScholarPubMed
Sato, M, Suzuki, M, Oshima, T, et al.Long-term follow-up of obstructive sleep apnea syndrome following surgery in children and adults. Tohoku J Exp Med. 2000; 192(3), 165–172.CrossRefGoogle ScholarPubMed
Shirakami, G, Nakao, K, Saito, Y, et al.Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats. Life Sci. 1991; 48(10), 969–976.CrossRefGoogle ScholarPubMed
Simonneau, G, Galiè, N, Rubin, LJ, et al.Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004; 43(12 Suppl S), 5S–12S.CrossRefGoogle ScholarPubMed
Ruijtenbeek, K, le Noble, FA, Janssen, GM, et al.Chronic hypoxia stimulates periarterial sympathetic nerve development in chicken embryo. Circulation. 2000; 102(23), 2892–2897.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Allison, BJ, et al.Maternal chronic hypoxia increases expression of genes regulating lung liquid movement and surfactant maturation in male fetuses in late gestation. J Physiol. 2017; 595(13), 4329–4350.CrossRefGoogle ScholarPubMed
McGillick, EV, Orgeig, S, Giussani, DA, Morrison, JL.Chronic hypoxaemia as a molecular regulator of fetal lung development: implications for risk of respiratory complications at birth. Paediatr Respir Rev. 2017; 21, 3–10.Google ScholarPubMed
Belik, J, Keeley, FW, Baldwin, F, Rabinovitch, M.Pulmonary hypertension and vascular remodeling in fetal sheep. Am J Physiol. 1994; 266(6 Pt 2), H2303–H2309.Google ScholarPubMed
Dodson, RB, Morgan, MR, Galambos, C, Hunter, KS, Abman, SH.Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep. Am J Physiol Lung Cell Mol Physiol. 2014; 307(11), L822–L828.CrossRefGoogle ScholarPubMed
Grover, TR, Parker, TA, Zenge, JP, Markham, NE, Kinsella, JP, Abman, SH.Intrauterine hypertension decreases lung VEGF expression and VEGF inhibition causes pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol. 2003; 284, L508–L517.CrossRefGoogle ScholarPubMed
Grover, TR, Parker, TA, Balasubramaniam, V, Markham, NE, Abman, SH.Pulmonary hypertension impairs alveolarization and reduces lung growth in the ovine fetus. Am J Physiol Lung Cell Mol Physiol. 2005; 288, L648–L654.CrossRefGoogle ScholarPubMed
Simon, MC.Mitochondrial reactive oxygen species are required for hypoxic HIF alpha stabilization. Adv Exp Med Biol. 2006; 588, 165–170.CrossRefGoogle ScholarPubMed
Franco Mdo, C, Dantas, AP, Akamine, EH, et al.Enhanced oxidative stress as a potential mechanism underlying the programming of hypertension in utero. J Cardiovasc Pharmacol. 2002; 40, 501–509.CrossRefGoogle ScholarPubMed
Hoshikawa, Y, Ono, S, Suzuki, S, et al.Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia. J Appl Physiol. 2001; 90, 1299–1306.CrossRefGoogle ScholarPubMed
Farrow, KN, Lakshminrusimha, S, Reda, WJ, et al.Superoxide dismutase restores eNOS expression and function in resistance pumonary arteries from neonatal lambs with persistent pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2008; 295(6), L979–L987.CrossRefGoogle Scholar
Afolayan, AJ, Eis, A, Teng, RJ, et al.Decreases in manganese superoxide dismutase expression and activity contribute to oxidative stress in persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol. 2012; 303(10), L870–L879.CrossRefGoogle ScholarPubMed
Afolayan, AJ, Eis, A, Alexander, M, et al.Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension. Am J Physiol Cell Mol Physiol. 2016; 310(1), L40–L49.CrossRefGoogle ScholarPubMed
Brain, KL, Allison, BJ, Niu, Y, et al.Intervention against hypertension in the next generation programmed by developmental hypoxia. PLoS Biol. 2019; 17(1), e2006552.CrossRefGoogle ScholarPubMed
Perez, M, Robbins, ME, Revhaug, C, Saugstad, OD.Oxygen radical disease in the newborn, revisited: oxidative stress and disease in the newborn period. Free Radic Biol Med. 2019; 142, 61–72.CrossRefGoogle ScholarPubMed
Herrera, EA, Macchiavello, R, Montt, C, et al.Melatonin improves cerebrovascular function and decreases oxidative stress in chronically hypoxic lambs. J Pineal Res. 2014; 57(1), 33–42.CrossRefGoogle ScholarPubMed
Astorga, CR, González-Candia, A, Candia, AA, et al.Melatonin decreases pulmonary vascular remodeling and oxygen sensitivity in pulmonary hypertensive newborn lambs. Front Physiol. 2018; 6–9, 185.CrossRefGoogle Scholar
Polglase, GR, Barbuto, J, Allison, BJ, et al.Effects of antenatal melatonin therapy on lung structure in growth-restricted newborn lambs. J Appl Physiol (1985); 123(5), 1195–1203.CrossRefGoogle Scholar
Castillo-Melendez, M, Yawno, T, Sutherland, A, Jenkin, G, Wallace, EM, Miller, SL.Effects of antenatal melatonin treatment on the cerebral vasculature in an ovine model of fetal growth restriction. Dev Neurosci. 2017; 39(1–4), 323–337.CrossRefGoogle Scholar
Tare, M, Parkington, HC, Wallace, EM, et al.Maternal melatonin administration mitigates coronary stiffness and endothelial dysfunction, and improves heart resilience to insult in growth restricted lambs. J Physiol. 2014; 592(12), 2695–2709.CrossRefGoogle ScholarPubMed
Aridas, JDS, Yawno, T, Sutherland, AE, et al.Systemic and transdermal melatonin administration prevents neuropathology in response to perinatal asphyxia in newborn lambs. J Pineal Res. 2018; 64(4), e12479.CrossRefGoogle ScholarPubMed
Gonzalez-Candia, A, Veliz, M, Carrasco-Pozo, C, et al.Antenatal melatonin modulates an enhanced antioxidant/pro-oxidant ratio in pulmonary hypertensive newborn sheep. Redox Biol. 2019; 22, 101128.CrossRefGoogle ScholarPubMed
Rudolph, AM.Fetal and neonatal pulmonary circulation. Annu Rev Physiol. 1979; 41, 383–395.CrossRefGoogle ScholarPubMed
Herrera, EA, Riquelme, RA, Ebensperger, G, et al.Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level. Am J Physiol Regul Integr Comp Physiol. 2010; 299(6), R1676–R1684.CrossRefGoogle ScholarPubMed
Jernigan, NL, Resta, TC.Calcium homeostasis and sensitization in pulmonary arterial smooth muscle. Microcirculation. 2014; 21(3), 259–271.CrossRefGoogle ScholarPubMed
Herrera, EA, Ebensperger, G, Hernández, I, Sanhueza, EM, Llanos, AJ, Reyes, RV.The role of nitric oxide signaling in pulmonary circulation of high- and low-altitude newborn sheep under basal and acute hypoxic conditions. Nitric Oxide. 2019; 89, 71–80.CrossRefGoogle ScholarPubMed
Reyes, RV, Castillo-Galán, S, Hernandez, I, Herrera, EA, Ebensperger, G, Llanos, AJ.Revisiting the role of TRP, orai, and ASIC channels in the pulmonary arterial response to hypoxia. Front Physiol. 2018; 9, 486.CrossRefGoogle ScholarPubMed
Shimoda, LA, Sylvester, JT, Booth, GM, et al.Inhibition of voltage gated K+ currents by endothelin-1 in human pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol. 2001; 281, L1115–L1122.CrossRefGoogle ScholarPubMed
Sylvester, JT, Shimoda, LA, Aaronson, PI, Ward, JP.Hypoxic pulmonary vasoconstriction. Physiol Rev. 2012; 92, 367–520.CrossRefGoogle ScholarPubMed
MacLean, MR, Deuchar, GA, Hicks, MN, et al.Overexpression of the 5-hydroxytryptamine transporter gene: effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension. Circulation. 2004; 109, 2150–2155.CrossRefGoogle ScholarPubMed
Long, L, MacLean, MR, Jeffery, TK, et al.Serotonin increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. Circ Res. 2006; 98, 818–827.CrossRefGoogle ScholarPubMed
Blood, AB, Terry, MH, Merritt, TA, et al.Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs. Am J Physiol Regul Integr Comp Physiol. 2013; 304(2), R136–R146.CrossRefGoogle ScholarPubMed
Delaney, C, Gien, J, Roe, G, Isenberg, N, Kailey, J, Abman, SH.Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn. Am J Physiol Lung Cell Mol Physiol. 2013; 304(12), L894–L901.CrossRefGoogle Scholar
Stenmark, KR, Frid, MG, Graham, BB, Tuder, RM.Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension. Cardiovasc Res. 2018; 114(4), 551–564.CrossRefGoogle ScholarPubMed
Fike, CD, Kaplowitz, MR, Zhang, Y, Pfister, SL. Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs. J Appl Physiol. 2005; 98, 1111–1118.CrossRefGoogle Scholar
Trow, TK, Taichman, DB.Endothelin receptor blockade in the management of pulmonary arterial hypertension: selective and dual antagonism. Respir Med. 2009; 103, 951–962.CrossRefGoogle ScholarPubMed
Fagan, KA, Oka, M, Bauer, NR, et al.Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am J Physiol Lung Cell Mol Physiol. 2004; 287, L656–L664.CrossRefGoogle ScholarPubMed
Broughton, BR, Walker, BR, Resta, TC.Chronic hypoxia induces Rho kinase-dependent myogenic tone in small pulmonary arteries. Am J Physiol Lung Cell Mol Physiol. 2008; 294, L797–L806.CrossRefGoogle ScholarPubMed
Tirosh, R, Resnik, ER, Herron, J, Sukovich, DJ, Hong, Z, Weir, EK, Cornfield DN. Acute normoxia increases fetal pulmonary artery endothelial cell cytosolic Ca2+ via Ca-2+induced Ca2+ release. Pediatr Res. 2006; 60, 258–263.CrossRefGoogle Scholar
Herrera, EA, Reyes, RV, Giussani, DA, et al.Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano. Cardiovasc Res. 2008; 77(1), 197–201.CrossRefGoogle ScholarPubMed
Lakshminrusimha, S, Porta, NF, Farrow, KN, et al.Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med. 2009; 10, 106–112.CrossRefGoogle ScholarPubMed
Pak, O, Aldashev, A, Welsh, D, Peacock, A.The effects of hypoxia on the cells of the pulmonary vasculature. Eur Respir J. 2007; 30, 364–372.CrossRefGoogle ScholarPubMed
Frid, MG, Brunetti, JA, Burke, DL, et al.Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am J Pathol. 2006; 168, 659–669.CrossRefGoogle ScholarPubMed
Desmouliere, A, Chaponnier, C, Gabbiani, G.Tissue repair, contraction, and the myofibroblast. Wound Repair Regen. 2005; 13, 7–12.CrossRefGoogle ScholarPubMed
Bedard, K, Krause, K-H.The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007; 87, 245–313.CrossRefGoogle ScholarPubMed
Ismail, S, Sturrock, A, Wu, P, et al.NOX4 mediates hypoxia-induced proliferation of human pulmonary artery smooth muscle cells: the role of autocrine production of transforming growth factor-β1 and insulin-like growth factor binding protein-3. Am J Physiol Lung Cell Mol Physiol. 2009; 296, L489–L499.CrossRefGoogle ScholarPubMed
Wang, M, Gu, S, Liu, Y, et al.miRNA-PDGFRB/HIF1A-lncRNA CTEPHA1 network plays important roles in the mechanism of chronic thromboembolic pulmonary hypertension. Int Heart J. 2019; 60(4), 924–937.CrossRefGoogle ScholarPubMed
Wu, W, Li, Y, Xu, DQ.Role of ROS/Kv/HIF axis in the development of hypoxia-induced pulmonary hypertension. Chin Med Sci J. 2017; 32(4), 253–259.Google ScholarPubMed
Bonnet, S, Boucherat, O, The ROS controversy in hypoxic pulmonary hypertension revisited. Eur Respir J. 2018; 8, 51(3). pii: 1800276.Google Scholar
Michelakis, ED, Hampl, V, Nsair, A, et al.Diversity in mitochondrial function explains differences in vascular oxygen sensing. Circ Res. 2002; 90, 1307–1315.CrossRefGoogle ScholarPubMed
Waypa, GB, Marks, JD, Mack, MM, et al.Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes. Circ Res. 2002; 91(8), 719–726.CrossRefGoogle ScholarPubMed
Aguilar, SA, Arias, PV, Canquil, I, et al.Melatonin modulates the expression of pulmonary prostanoids. Rev Med Chil. 2019; 147(3), 281–288.CrossRefGoogle ScholarPubMed
Humbert, M, Guignabert, C, Bonnet, S, et al.Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019; 53(1), 1801887.CrossRefGoogle ScholarPubMed
Hanson, MA, Gluckman, PD.Early developmental conditioning of later health and disease: physiology or pathophysiology. Physiol Rev. 2014; 94(4), 1027–1076.CrossRefGoogle ScholarPubMed
Yang, Q, Lu, Z, Ramchandran, R, Longo, LD, Raj, JU.Pulmonary artery smooth muscle cell proliferation and migration in fetal lambs acclimatized to high-altitude long-term hypoxia: role of histone acetylation. Am J Physiol Lung Cell Mol Physiol. 2012; 303(11), L1001–L1010.CrossRefGoogle ScholarPubMed
Ke, X, Johnson, H, Jing, X, et al.Persistent pulmonary hypertension alters the epigenetic characteristics of endothelial nitric oxide synthase gene in pulmonary artery endothelial cells in a fetal lamb model. Physiol Genomics. 2018; 50(10), 828–836.CrossRefGoogle Scholar
Kim, GH, Ryan, JJ, Marsboom, G, Archer, SL.Epigenetic mechanisms of pulmonary hypertension. Pulm Circ. 2011; 1(3), 347–356.CrossRefGoogle ScholarPubMed
Dodd, IB, Micheelsen, MA, Sneppen, K, Thon, G.Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell. 2007; 129(4), 813–822.CrossRefGoogle ScholarPubMed
Chang, G, Mouillet, JF, Mishima, T, et al.Expression and trafficking of placental microRNAs at the feto-maternal interface. FASEB J. 2017; 31(7), 2760–2770.CrossRefGoogle ScholarPubMed
Huo, H, Luo, Z, Wang, M, et al.MicroRNA expression profile in intrauterine hypoxia-induced pulmonary hypoplasia in rats. Exp Ther Med. 2014; 8(3), 747–753.CrossRefGoogle ScholarPubMed
Zhuang, Y, Dai, J, Wang, Y, et al.MiR-338* targeting smoothened to inhibit pulmonary fibrosis by epithelial-mesenchymal transition. Am J Transl Res. 2016; 8(7), 3206–3213.Google ScholarPubMed
Xu, X, Wang, S, Liu, J, et al.Hypoxia induces downregulation of soluble guanylyl cyclase β1 by miR-34c-5p. J Cell Sci. 2012; 125(Pt 24), 6117–6126.CrossRefGoogle ScholarPubMed
Pasquini, G, Kunej, T.A map of the microRNA regulatory networks identified by experimentally validated microRNA-target interactions in five domestic animals: cattle, pig, sheep, dog, and chicken. OMICS. 2019; 23(9), 448–456.CrossRefGoogle Scholar
Rashid, N, Morin, FC 3rd, Swartz, DD, et al.Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation. Pediatr Res. 2006; 60(5), 624–629.CrossRefGoogle ScholarPubMed
Chandrasekar, I, Eis, A, Konduri, GG.Betamethasone attenuates oxidant stress in endothelial cells from fetal lambs with persistent pulmonary hypertension. Pediatr Res. 2008; 63(1), 67–72.CrossRefGoogle ScholarPubMed
Orgeig, S, McGillick, EV, Botting, KJ, Zhang, S, McMillen, IC, Morrison, JL.Increased lung prolyl hydroxylase and decreased glucocorticoid receptor are related to decreased surfactant protein in the growth-restricted sheep fetus. Am J Physiol Lung Cell Mol Physiol. 2015; 309(1), L84–L97.CrossRefGoogle ScholarPubMed
Xue, Q, Ducsay, CA, Longo, LD, Zhang, L.Effect of long-term high-altitude hypoxia on fetal pulmonary vascular contractility. J Appl Physiol (1985). 2008; 104(6), 1786–1792.CrossRefGoogle ScholarPubMed