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  • Chang, Ya-TingKarolinska Institutet (author)

Antenatal imatinib treatment reduces pulmonary vascular remodeling in a rat model of congenital diaphragmatic hernia

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • American Physiological Society,2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-177607
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-177607URI
  • https://doi.org/10.1152/ajplung.00325.2010DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:124785785URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

  • pulmonary hypertension
  • PDGF

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ringman Uggla, Andreas (author)
  • Österholm, CeciliaKarolinska Institutet (author)
  • Tran, Phan-KietUppsala universitet,Thoraxkirurgi (author)
  • Eklöf, Ann-Christine (author)
  • Lengquist, MarietteKarolinska Institutet (author)
  • Hedin, UlfKarolinska Institutet (author)
  • Tran-Lundmark, KarinKarolinska Institutet (author)
  • Frenckner, BjörnKarolinska Institutet (author)
  • Karolinska InstitutetThoraxkirurgi (creator_code:org_t)

Related titles

  • In:American Journal of Physiology - Lung cellular and Molecular Physiology: American Physiological Society302:11, s. L1159-L11661040-06051522-1504

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