scholarly journals Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0159005 ◽  
Author(s):  
Csaba Galambos ◽  
Angela D. Minic ◽  
Douglas Bush ◽  
Dominique Nguyen ◽  
Blair Dodson ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Potential Role ◽  
Angiogenic Factors ◽  
Vascular Growth

scholarly journals Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service

2014 ◽  
Vol 32 (2) ◽  
pp. 159-163 ◽  
Author(s):  
Felipe Alves Mourato ◽  
Lúcia Roberta R. Villachan ◽  
Sandra da Silva Mattos
Keyword(s):  
Congenital Heart Disease ◽  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Heart Disease ◽  
Congenital Heart ◽  
Septal Defect ◽  
Heart Diseases ◽  
Heart Defects ◽  
Descriptive Analysis ◽  
Atrioventricular Septal Defect

OBJECTIVE:To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis.METHODS:Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7.RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age.CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension.

scholarly journals Targeting Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension (BPD-PH): Potential Role of the FGF Signaling Pathway in the Development of the Pulmonary Vascular System

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1875
Author(s):  
Cho-Ming Chao ◽  
Lei Chong ◽  
Xuran Chu ◽  
Amit Shrestha ◽  
Judith Behnke ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Signaling Pathway ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Potential Role ◽  
Vascular System ◽  
Point Of View ◽  
Pulmonary Vasculature ◽  
Curative Therapy

More than 50 years after the first description of Bronchopulmonary dysplasia (BPD) by Northway, this chronic lung disease affecting many preterm infants is still poorly understood. Additonally, approximately 40% of preterm infants suffering from severe BPD also suffer from Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH), leading to a significant increase in total morbidity and mortality. Until today, there is no curative therapy for both BPD and BPD-PH available. It has become increasingly evident that growth factors are playing a central role in normal and pathologic development of the pulmonary vasculature. Thus, this review aims to summarize the recent evidence in our understanding of BPD-PH from a basic scientific point of view, focusing on the potential role of Fibroblast Growth Factor (FGF)/FGF10 signaling pathway contributing to disease development, progression and resolution.

scholarly journals Angiogenic profile identifies pulmonary hypertension in children with Down syndrome

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986654 ◽  
Author(s):  
Douglas Bush ◽  
Kristine Wolter-Warmerdam ◽  
Brandie D. Wagner ◽  
Csaba Galambos ◽  
D.Dunbar Ivy ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Down Syndrome ◽  
Classification Tree ◽  
Children With Down Syndrome ◽  
Angiogenic Proteins ◽  
Peptide Signals ◽  
Low Levels ◽  
Cardiac Catheterizations ◽  
A Prospective Study ◽  
Hypertension In Children

Past studies have shown that lung angiogenic signaling may be abnormal in children with Down syndrome, but whether differences in circulating angiogenic proteins can identify pulmonary hypertension in children with Down syndrome is unknown. A prospective study of 78 children from birth to 21 years of age was conducted to evaluate clinical data, echocardiograms, and cardiac catheterizations. Four patient populations were enrolled, including children with Down syndrome who have pulmonary hypertension (Down syndrome + pulmonary hypertension, n = 12); control children without Down syndrome who have pulmonary hypertension (C + pulmonary hypertension, n = 15); children with Down syndrome without a known diagnosis of pulmonary hypertension (Down syndrome − pulmonary hypertension, n = 26); and children without Down syndrome or a known diagnosis of pulmonary hypertension (C − pulmonary hypertension, n = 25). Blood samples were collected at enrollment and concentrations for 11 proteins were evaluated. A classification tree was created to identify angiogenic peptide signals that may be associated with pulmonary hypertension in children with Down syndrome compared with controls. Findings identified elevated endostatin levels (>4.98 log10 pg/ml) were associated with Down syndrome. Platelet-derived growth factor AA levels (>2.51 log10 pg/ml) were higher in non-Down syndrome patients with pulmonary hypertension (C + pulmonary hypertension), whereas lower angiogenin (<5.428 log10 pg/ml) or lower angiogenin with elevated angiopoietin-1 levels (>3.59 log10 pg/ml) distinguished pulmonary hypertension in those with Down syndrome from the other groups. This study suggests that children with Down syndrome have high endostatin levels, but low levels of angiogenin levels in children with Down syndrome more often identified pulmonary hypertension than Down syndrome subjects without pulmonary hypertension or non-Down syndrome children. We speculate that these changes in circulating peptides support the concept of dysregulated angiogenesis in children with Down syndrome and pulmonary hypertension, which may further support potential utility as biomarkers for identifying subjects with Down syndrome at risk for pulmonary hypertension in this population.

Angiogenic Gene Expression in Down Syndrome Fetal Hearts

2015 ◽  
Vol 40 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Olga Sánchez ◽  
Carmen Domínguez ◽  
Aina Ruiz ◽  
Irene Ribera ◽  
Jaume Alijotas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Growth Factor ◽  
Heart Defects ◽  
Hypoxia Inducible Factor ◽  
Transcript Level ◽  
Heart Tissue ◽  
Angiogenic Factors ◽  
Heme Oxygenase 1 ◽  
Endothelial Growth Factor

Introduction: Forty percent of Down syndrome (DS) fetuses have congenital heart defects (CHD). An abnormal angiogenic environment has been described in euploid fetuses with CHD. However, the underlying pathophysiologic pathway that contributes to CHD in DS remains unknown. The objective was to compare the expression of angiogenic factors and chronic hypoxia genes in heart tissue from DS and euploid fetuses with and without CHD. Methods: The gene expression profile was determined by real-time PCR quantification in heart tissue from 33 fetuses with DS, 23 euploid fetuses with CHD and 23 control fetuses. Results: Angiogenic factors mRNA expression was significantly increased in the DS group compared to the controls (soluble fms-like tyrosine kinase-1, 81%, p = 0.007; vascular endothelial growth factor A, 57%, p = 0.006, and placental growth factor, 32%, p = 0.0227). Significant increases in the transcript level of hypoxia-inducible factor-2α and heme oxygenase 1 were also observed in the DS group compared to the controls. The expression of angiogenic factors was similar in DS fetuses and CHD euploid fetuses with CHD. Conclusion: Abnormal angiogenesis was detected in the hearts of DS fetuses with and without CHD. Our results suggest that DS determines an intrinsically angiogenic impairment that may be present in the fetal heart.

scholarly journals Purinergic dysregulation in pulmonary hypertension

2016 ◽  
Vol 311 (1) ◽  
pp. H286-H298 ◽  
Author(s):  
Scott H. Visovatti ◽  
Matthew C. Hyman ◽  
Sascha N. Goonewardena ◽  
Anuli C. Anyanwu ◽  
Yogendra Kanthi ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Potential Role ◽  
Purinergic Signaling ◽  
Continuous Administration ◽  
P2x1 Receptor ◽  
Pulmonary Endothelium ◽  
Pulmonary Arterial ◽  
Medial Hypertrophy

Despite the fact that nucleotides and adenosine help regulate vascular tone through purinergic signaling pathways, little is known regarding their contributions to the pathobiology of pulmonary arterial hypertension, a condition characterized by elevated pulmonary vascular resistance and remodeling. Even less is known about the potential role that alterations in CD39 (ENTPD1), the ectonucleotidase responsible for the conversion of the nucleotides ATP and ADP to AMP, may play in pulmonary arterial hypertension. In this study we identified decreased CD39 expression on the pulmonary endothelium of patients with idiopathic pulmonary arterial hypertension. We next determined the effects of CD39 gene deletion in mice exposed to normoxia or normobaric hypoxia (10% oxygen). Compared with controls, hypoxic CD39−/− mice were found to have a markedly elevated ATP-to-adenosine ratio, higher pulmonary arterial pressures, more right ventricular hypertrophy, more arterial medial hypertrophy, and a pro-thrombotic phenotype. In addition, hypoxic CD39−/− mice exhibited a marked increase in lung P2X1 receptors. Systemic reconstitution of ATPase and ADPase enzymatic activities through continuous administration of apyrase decreased pulmonary arterial pressures in hypoxic CD39−/− mice to levels found in hypoxic CD39+/+ controls. Treatment with NF279, a potent and selective P2X1 receptor antagonist, lowered pulmonary arterial pressures even further. Our study is the first to implicate decreased CD39 and resultant alterations in circulating purinergic signaling ligands and cognate receptors in the pathobiology of pulmonary arterial hypertension. Reconstitution and receptor blocking experiments suggest that phosphohydrolysis of purinergic nucleotide tri- and diphosphates, or blocking of the P2X1 receptor could serve as treatment for pulmonary arterial hypertension. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/purinergic-dysregulation-in-pulmonary-hypertension/ .

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