Expression of HIF-1α, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia

Lemus-Varela, M.L.; Flores-Soto, M.E.; Cervantes-Munguía, Ramón; Torres-Mendoza, Blanca Miriam; Gudiño-Cabrera, Graciela; Chaparro-Huerta, V.; Ortuño-Sahagún, Daniel; Beas‐Zárate, Carlos

doi:10.1016/j.clinbiochem.2009.09.022

Cited by 57 publications

(35 citation statements)

References 36 publications

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“…HIF-1α mRNA expression is increased in newborn infants with persistent pulmonary hypertension and congenital cyanotic cardiac disorders as well as the expression of its target genes VEGF and Epo [25]. Both factors are controlled by HIFs and the activity of prolyl hydroxylase domain proteins.…”

Section: Discussionmentioning

confidence: 99%

Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses

Sweetman

Onwuneme²,

Watson³

et al. 2016

Neonatology

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Background: Infants with neonatal encephalopathy (NE) of hypoxic-ischaemic origin are at risk of oxidative and ischaemia-reperfusion injury, which may induce abnormal inflammatory responses involving excessive cytokine production and release in serum and cerebrospinal fluid (CSF). Systemic inflammation is found in infants with NE, and we therefore were interested in cytokines associated with hypoxia, including vascular endothelial growth factor (VEGF) and erythropoietin (Epo). Objective: To investigate the relationship between Epo, VEGF levels, brain injury and outcome in a group of term infants exposed to perinatal asphyxia (PA) compared to controls. Methods: Serum and CSF biomarkers associated with hypoxia (VEGF, Epo) were serially measured using multiplex immunoassays over days 1-4 in term infants exposed to PA including infants with NE and controls. Results were compared to severity of encephalopathy, MR brain imaging and mortality. Results: Ninety-four infants had 247 serum samples collected (n = 12 controls, 82 exposed to PA with 34 CSF samples), and 4 infants died. Controls had significantly lower serum Epo levels on days 1 and 2 compared to those exposed to PA (p = 0.02). Grade II/III NE was significantly associated with elevated day 2 Epo and decreased day 1 VEGF (p < 0.05; day 2 Epo AUC = 0.74, cut-off 10.05 IU/ml). Elevated serum Epo was associated with severely abnormal MRI. Mortality was associated with elevated day 3 Epo and decreased day 1 VEGF. CSF levels were all after hypothermia and were not significantly associated with outcome. Conclusion: Serum Epo and VEGF may be markers of severity of hypoxia-ischaemia and brain injury as they are closely related to hypoxic exposure.

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Section: Discussionmentioning

confidence: 99%

Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses

Sweetman

Onwuneme²,

Watson³

et al. 2016

Neonatology

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“…In addition, mRNA level of HIF-1α as well as that of two of its representative target genes, VEGF and EPO, were found to be upregulated in blood samples of newborns with cyanosis and persistent pulmonary hypertension, therefore representing early markers of generalized hypoxia [36]. If the HIF-1α/VEGF-induced collateral vessel formation in hypoxemic myocardium is essential to compensate the lack of oxygen supply in cyanotic hearts, especially in cases of coarctation of aorta, an abnormal vessel formation can become a source of morbidity, due to arteriovenous malformations [34].…”

Section: Hif-1alpha Mediated Angiogenic Responsementioning

confidence: 99%

Hypoxia-Induced Molecular and Cellular Changes in the Congenitally Diseased Heart: Mechanisms and Strategies of Intervention

Iacobazzi¹,

Caputo²,

Ghorbel³

2017

Hypoxia and Human Diseases

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Tissue hypoxia plays a critical role in the pathobiology of congenital heart diseases, especially with regard to cyanotic patients. Here, we describe the cellular and molecular mechanisms induced by hypoxia in the diseased heart, with particular attention to the metabolic and functional changes that underlie the hypoxia-induced right ventricle remodelling. The role of reactive oxygen species in transcriptomic changes, DNA damage, contractile dysfunction and extracellular matrix remodelling will be addressed. Furthermore, the reoxygenation injury, which occurs when oxygen is reintroduced upon initiation of cardiopulmonary bypass, will be discussed. This allows a better understanding of the risks associated with the reoxygenation injury in children undergoing openheart surgery and helps to improve strategies of intervention for myocardial protection.

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“…Another potent stimulator of angiogenesis, EC apoptosis and cell arrest is hypoxia. Quite commonly found in various CHDs (110,111), hypoxia may also have an influence on the angiogenic processes in affected children. Indeed, hypoxia has been shown to regulate the expression of different miRs, which have been identified in several cancer cell lines or ECs (112)(113)(114).…”

Section: Regulation Of Angiogenesismentioning

confidence: 99%

MicroRNAs: pleiotropic players in congenital heart disease and regeneration

et al. 2017

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Congenital heart disease (CHD) is the leading cause of infant death, affecting approximately 4-14 live births per 1,000. Although surgical techniques and interventions have improved significantly, a large number of infants still face poor clinical outcomes. MicroRNAs (miRs) are known to coordinately regulate cardiac development and stimulate pathological processes in the heart, including fibrosis or hypertrophy and impair angiogenesis. Dysregulation of these regulators could therefore contribute (I) to the initial development of CHD and (II) at least partially to the observed clinical outcomes of many CHD patients by stimulating the aforementioned pathways. Thus, miRs may exhibit great potential as therapeutic targets in regenerative medicine. In this review we provide an overview of miR function and elucidate their role in selected CHDs, including hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), ventricular septal defects (VSDs) and Holt-Oram syndrome (HOS). We then bridge this knowledge to the potential usefulness of miRs and/or their targets in therapeutic strategies for regenerative purposes in CHDs.

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Expression of HIF-1α, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia

Cited by 57 publications

References 36 publications

Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses

Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses

Hypoxia-Induced Molecular and Cellular Changes in the Congenitally Diseased Heart: Mechanisms and Strategies of Intervention

MicroRNAs: pleiotropic players in congenital heart disease and regeneration

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