Chronic hypoxia increases peroxynitrite, MMP9 expression, and collagen accumulation in fetal guinea pig hearts

Evans, LaShauna C.; Liu, Hongshan; Pinkas, Gerard A.; Thompson, Loren P.

doi:10.1038/pr.2011.10

Cited by 48 publications

(51 citation statements)

References 39 publications

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“…68 Alternatively, posttranslational modification can occur by direct inhibition of CCO activity by nitric oxide, 69,70 peroxynitrite, 71 malondialdehyde, 72 and acetylation of lysine residues. 73 Thus, the elevated nitric oxide, peroxynitrite, and malondialdehyde levels measured in HPX fetal guinea pig hearts in our previous studies 6,7 may be the initiating factors in generating a sustained decrease in CCO activity in the offspring. Previous studies have shown that both peroxynitrite and malondialdehyde can form adducts with mitochondrial complex activity in I, II, and V 71 and CCO, 72 respectively, to inhibit mitochondrial enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7]34 Offspring guinea pigs exposed to prenatal HPX (n ¼ 9) had significantly (P < .05) greater systolic (59.2 + 4.0 vs 72.3 + 2.3 mm Hg, NMX vs HPX, respectively), diastolic (41.9 + 3.4 vs 51.1 + 1.8 mm Hg), and mean arterial blood pressures (47.1 + 3.6 vs 58.2 + 1.9 mm Hg) than that of NMX controls (n ¼ 6). The arterial blood pressures of NMX are representative of values measured in anesthetized adult guinea pigs.…”

Section: Animal Parametersmentioning

confidence: 99%

“…26 The role of prenatal HPX on fetal cardiac mitochondrial function has had limited attention. We have reported that chronic maternal HPX of pregnant guinea pigs generates increases in fetal cardiac HPX-inducible factor (HIF-1a), 6 peroxynitrite, 7 and malondialdehyde levels, 27 indicative of HPX stress. Further, we have shown that chronic HPX generates oxidative and nitrosative stress within fetal heart ventricles, 7 concomitant with reduced cardiac CCO activity.…”

Section: Introductionmentioning

confidence: 99%

“…We have reported that chronic maternal HPX of pregnant guinea pigs generates increases in fetal cardiac HPX-inducible factor (HIF-1a), 6 peroxynitrite, 7 and malondialdehyde levels, 27 indicative of HPX stress. Further, we have shown that chronic HPX generates oxidative and nitrosative stress within fetal heart ventricles, 7 concomitant with reduced cardiac CCO activity. 27 Therefore, chronic HPX has a negative impact on fetal cardiac mitochondrial function although its lasting consequences on cardiac function in the offspring remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts

2014

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Prenatal hypoxia (HPX) reduces mitochondrial cytochrome c oxidase (CCO and COX) activity in fetal guinea pig (GP) hearts. The aim of this study was to quantify the lasting effects of chronic prenatal HPX on cardiac mitochondrial enzyme activity and protein expression in offspring hearts. Pregnant GPs were exposed to either normoxia (NMX) or HPX (10.5%O 2 ) during the last 14 days of pregnancy. Both NMX and HPX fetuses, delivered vaginally, were housed under NMX conditions until 90 days of age. Total RNA and mitochondrial fractions were isolated from hearts of anesthetized NMX and HPX offspring and showed decreased levels of CCO but not medium-chain acyl dehydrogenase activity, protein levels of nuclear-and mitochondrial-encoded COX4 and COX1, respectively, and messenger RNA expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, COX5b, and 4.1 compared to NMX controls. Prenatal HPX may alter mitochondrial function in the offspring by disrupting protein expression associated with the respiratory chain.

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Section: Discussionmentioning

confidence: 99%

Section: Animal Parametersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts

2014

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“…Additionally, Giussani and colleagues (2012) (Evans et al, 2012) exposed to prenatal hypoxia. Increased renal oxidative stress has also been reported in chronic cigarette exposure in utero (Stangenberg et al, 2015).…”

Section: Mechanisms Of Hypoxia-induced Damage and Avenues For Intervementioning

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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Nitric oxide synthase and changes in oxidative stress levels in embryonic kidney observed in a rabbit model of intrauterine growth restriction

et al. 2016

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Chronic hypoxia increases peroxynitrite, MMP9 expression, and collagen accumulation in fetal guinea pig hearts

Cited by 48 publications

References 39 publications

Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts

Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts

Gestational hypoxia and programming of disease

Nitric oxide synthase and changes in oxidative stress levels in embryonic kidney observed in a rabbit model of intrauterine growth restriction

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