| Title |
Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia
|
|---|---|
| Published in |
Molecular Medicine, November 2011
|
| DOI | 10.2119/molmed.2011.00210 |
| Pubmed ID | |
| Authors |
Cristina Nogueira-Silva, Emanuel Carvalho-Dias, Paulina Piairo, Susana Nunes, Maria J. Baptista, Rute S. Moura, Jorge Correia-Pinto |
| Abstract |
Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT₁) and type 2 (AT₂) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT₁ receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT₂-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT₂ receptor is presented as a putative antenatal therapy for CDH. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 9 | 24% |
| Student > Ph. D. Student | 6 | 16% |
| Researcher | 5 | 14% |
| Student > Doctoral Student | 4 | 11% |
| Student > Bachelor | 2 | 5% |
| Other | 7 | 19% |
| Unknown | 4 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 21 | 57% |
| Agricultural and Biological Sciences | 6 | 16% |
| Biochemistry, Genetics and Molecular Biology | 3 | 8% |
| Engineering | 2 | 5% |
| Chemistry | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 3 | 8% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 November 2011.
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#18,301,870
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Outputs from Molecular Medicine
#900
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#194,698
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Outputs of similar age from Molecular Medicine
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