Cardiac and vascular disease prior to hatching in chick embryos incubated at high altitude

Salinas, Carlos; Blanco, Carlos E.; Villena, Mercedes; Camm, Emily J.; Tuckett, J. D.; Weerakkody, Ruwan; Kane, Andrew D.; Shelley, Anne-Marie; Wooding, F. B. P.; Quy, Mai Trinh; Giussani, Dino A.

doi:10.1017/s2040174409990043

Cited by 34 publications

(41 citation statements)

References 39 publications

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“…Several studies have now reported in mammalian and nonmammalian species that chronic developmental hypoxia can lead to an increase in the wall-to-lumen thickness or area ratio [27,28,33,34]. On the basis of hemodynamics, Folkow [47] stressed a role for an increased vascular wall-to-lumen ratio to be associated with an increase in resistance to flow and, thereby, an increase in perfusion pressure.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have employed the chick embryo as an animal model in an attempt to isolate the effects on growth and the developing cardiovascular system of chronic hypoxia, independent of changes in maternal nutrition and of the physiology of the mother and the placenta [28,29,30,31,32,33,34]. In mammals, only one previous study reported the relative contributions of developmental hypoxia and undernutrition to fetal alterations in somatic growth and cardiovascular structure and function in the rat [27].…”

Section: Introductionmentioning

confidence: 99%

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Morphological and Functional Alterations in the Aorta of the Chronically Hypoxic Fetal Rat

et al. 2011

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In human pregnancy, reduced placental perfusion has been associated with fetal aortic thickening. However, the relative contributions of fetal undernutrition versus fetal underoxygenation to triggering alterations in fetal cardiovascular development remain uncertain. Here, we isolate the effects of chronic fetal hypoxia on fetal cardiovascular development in a specific rodent model of chronic fetal hypoxia independent of changes in nutrition during pregnancy. Pregnant rats were housed under normoxic (21% O₂) or hypoxic (13% O₂) conditions from day 6 to day 20 of gestation. At day 20, pups and placentas were weighed. Fetal thoraces were fixed for quantitative histological analysis of the aorta. In a separate group, fetal aortic reactivity was assessed via in vitro wire myography. The experiments controlled for sex and within-litter variation. Placental weight was increased and fetal weight maintained in hypoxic pregnancy. Hypoxic pregnancy led to a 176% increment in wall thickness and a 170% increment in the wall-to-lumen area ratio of the fetal aorta. Fetal aortic vascular reactivity was markedly impaired, showing reduced constrictor and relaxant responsiveness in hypoxic pregnancy. Chronic developmental hypoxia independent of changes in nutrition has profound effects on the morphology and function of the fetal aorta in a mammalian species.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Morphological and Functional Alterations in the Aorta of the Chronically Hypoxic Fetal Rat

et al. 2011

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“…These responses were coupled with pump dysfunction, decreased ejection fractions, and diastolic dysfunction, which persisted in adulthood. Further, Salinas et al showed marked cardiovascular morphostructural changes in high-altitude chicks, which were reverted either by incubation at low altitude or by oxygen supplementation [26]. Notably, Herrera et al followed up these chicks to adulthood describing cardiac impairment in the capacity to response to pressor challenges [27].…”

Section: Fetal Growth Restrictionmentioning

confidence: 99%

“…Using avian models of FGR has served to establish that chronic hypoxia, independent of nutrition, plays a crucial role in vascular programming [30,31]. Studies of vascular function during fetal life show remarkable similarities between the effect of hypoxia in chick embryos and placental insufficiency in mammals [26,28]; they have also served to assess the long-term consequences [27]. In both cases (chick embryos and mammalian fetuses), the presence of endothelial dysfunction and vascular remodeling is observed mainly in peripheral arteries.…”

Section: Hypoxia and Oxidative Stress In Fgrmentioning

confidence: 99%

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Casanello¹,

Herrera²,

Krause³

2017

Hypoxia and Human Diseases

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Most of the worldwide deaths in patients with non-communicable diseases are due to cardiovascular and metabolic diseases, which are determined by a mix of environmental, genetic and epigenetic factors, and by their interactions. The aetiology of most cardiovascular diseases has been partially linked with in utero adverse conditions that may increase the risk of developing diseases later in life, known as Developmental Origins of Health and Disease (DOHaD). Perinatal hypoxia can program the fetal and postnatal developmental patterns, resulting in permanent modifications of cells, organs and systems function. In spite of the vast evidence obtained from human and animal studies linking development under adverse intrauterine conditions with increased cardiovascular risk, still few is known about the specific effects of intrauterine oxygen deficiency and the related pathogenic mechanisms. Currently, the most accepted processes that program cellular function are epigenetic mechanisms which determine gene expression in a cell-specific fashion. In this chapter we will review the current literature regarding the perinatal exposure to chronic hypoxia and Fetal Growth Restriction (FGR) in humans and animals and how this impinges the cardiovascular physiology through epigenetic, biochemical, morphologic and pathophysiologic modifications that translate into diseases blasting at postnatal life.

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“…It has been reported that chronic gestational hypoxia increases fetal cardiac afterload, which places strain on the heart and associated vessels. As a result, ventricular aortic thickening has been reported in chicks (Rouwet et al, 2002;Salinas et al, 2010) and rats exposed to chronic prenatal hypoxia Giussani et al, 2012b).…”

Section: Effects Of Prenatal Hypoxia On the Heartmentioning

confidence: 99%

Gestational hypoxia and programming of disease

Walton¹

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Fetal hypoxia remains the most common complication throughout pregnancy and has a wide aetiology including, but not limited to, placental insufficiency, high altitude living and maternal factors such as smoking and pulmonary disease. Intrauterine growth restriction and subsequent low birth weight are common features of pregnancies complicated by reduced oxygenation. Suboptimal organ development may arise, thereby substantially increasing vulnerability to cardiovascular and renal diseases in adulthood. Recently it has been established that prenatally programmed vulnerability to disease may be exacerbated by a postnatal 'second-hit', such as a high salt diet or ageing. The primary aim of this thesis was to investigate the effects of maternal hypoxia on the programming of cardiovascular and renal disease in mice, and secondly whether excess dietary salt intake throughout life may exacerbate disease outcomes.Pregnant CD1 mice were housed in a hypoxia chamber set to 12% oxygen throughout the last five days of pregnancy, from embryonic day (E) 14.5 until birth (P0). Control animals remained in normoxic room conditions (21% oxygen) throughout pregnancy. Upon littering, animals were removed from the hypoxia chamber and raised in normoxic room conditions. A subset of mice was fed a high salt diet from 10 weeks of age until post-mortem. Mice were housed in metabolic cages for 24 hours to assess renal function under basal conditions, and in response to a 24 hour water deprivation challenge, at 4 and 12 months of age. Blood pressure and microvascular function and structure were assessed in offspring at 12 months of age.Kidneys, hearts and aortas were collected for stereological and histological analyses.Prenatal hypoxia reduced nephron number in the kidneys of male offspring, leading to glomerular hypertrophy, renal fibrosis and mild albuminuria by 12 months of age. However, female offspring exposed to the same hypoxic insult in utero presented with normal number of glomeruli and renal pathology equivalent to control animals by 12 months of age. Both male and female hypoxia-exposed offspring had elevated mean arterial pressure at 12 months of age. A high salt diet throughout adult life increased cardiac tissue fibrosis, particularly in male hypoxia-exposed offspring, and exacerbated renal pathology in male hypoxia-exposed offspring only. Pressurized myography was performed at the time of post-mortem to assess functional, structural and mechanical properties of mesenteric resistance arteries at 12 months of age. Both male and female offspring exposed to maternal hypoxia had significantly 3 impaired endothelial function, which was not exacerbated by the high salt diet. The combination of prenatal hypoxia and a postnatal high salt diet caused marked stiffening of the microvasculature as well as loss of elastin integrity and increased collagen content in the aorta, consistent with vascular stiffness. This suggests that kidneys from female offspring are somehow protected from the in utero insult; however, this protection...

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Cardiac and vascular disease prior to hatching in chick embryos incubated at high altitude

Cited by 34 publications

References 39 publications

Morphological and Functional Alterations in the Aorta of the Chronically Hypoxic Fetal Rat

Morphological and Functional Alterations in the Aorta of the Chronically Hypoxic Fetal Rat

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Gestational hypoxia and programming of disease

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