uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
Show others and affiliations
2012 (English)In: American Journal of Physiology - Lung cellular and Molecular Physiology, ISSN 1040-0605, E-ISSN 1522-1504, Vol. 302, no 11, L1159-L1166 p.Article in journal (Refereed) Published
Abstract [en]

The pathophysiology of congenital diaphragmatic hernia (CDH) is constituted by pulmonary hypoplasia and pulmonary hypertension (PH). We previously reported successful treatment with imatinib of a patient with CDH. This study examines the effect of antenatal imatinib administration on the pulmonary vasculature in a rat model of CDH. Pregnant rats were given nitrofen to induce CDH. Controls were given olive oil. Half of the CDH fetuses and half of the controls were treated with imatinib antenatally E17-E21, rendering four groups: Control, Control+Imatinib, CDH, and CDH+Imatinib. Lung sections were obtained for morphometry and immunohistochemistry, and protein was purified for Western blot. Effects of nitrofen and imatinib on Ki-67, caspase-3, PDGF-B, and PDGF receptors were analyzed. Imatinib significantly reduced medial wall thickness in pulmonary arteries of rats with CDH. It also normalized lumen area and reduced the proportion of fully muscularized arteries. Imatinib also caused medial thinning in the control group. Cell proliferation was increased in CDH, and this proliferation was significantly reduced by imatinib. PDGF-B and PDGFR-beta were upregulated in CDH, and imatinib treatment resulted in a downregulation. PDGFR-alpha remained unchanged in CDH but was significantly downregulated by imatinib. Antenatal imatinib treatment reduces development of medial wall thickness and restores lumen area in pulmonary arteries in nitrofen-induced CDH. The mechanism is reduced cell proliferation. Imatinib is an interesting candidate for antenatal therapy for PH in CDH, but potential side effects need to be investigated and more specific targeting of PDGF signaling is needed.

Place, publisher, year, edition, pages
2012. Vol. 302, no 11, L1159-L1166 p.
Keyword [en]
pulmonary hypertension, PDGF
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-177607DOI: 10.1152/ajplung.00325.2010ISI: 000305420600004OAI: oai:DiVA.org:uu-177607DiVA: diva2:541430
Available from: 2012-07-17 Created: 2012-07-17 Last updated: 2012-07-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
Thoracic Surgery
In the same journal
American Journal of Physiology - Lung cellular and Molecular Physiology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 298 hits
ReferencesLink to record
Permanent link

Direct link