Receptor tyrosine kinase inhibitors in rodent pulmonary hypertension

Liliana Moreno-Vinasco, Joe G.N. Garcia

Research output: Chapter in Book/Report/Conference proceedingConference contribution

6 Scopus citations

Abstract

Pulmonary hypertension (PH) is a disorder characterized by vascular remodeling and proliferation, a phenotype dependent upon unimpeded growth factor and kinase pathway activation with strong similarities to malignant tumors. This chapter details our novel application of the multikinase inhibitor, sorafenib, in rodent models of PH to improved hemodynamic parameters and attenuates PH structural changes1. Sorafenib is a Raf kinase inhibitor and our biochemical and genomic evidence supported the potential involvement of the MAPK cascade system and TGFB3 in PH development and the response to therapy. Integration of expression genomic analyses coupled with intense bioinformatics identified gene expression and ontology signatures in the development of PH and implicated the role of cytoskeletal protein such as caldesmon or nmMLCK as potentially key participants in PH-induced vascular remodeling and proliferation. Our studies suggest the PKI sorafenib as a potentially novel treatment for severe PH with the MAPK cascade a potential canonical target profoundly effecting vascular cytoskeletal rearrangements and remodeling1.

Original languageEnglish (US)
Title of host publicationMembrane Receptors, Channels and Transporters in Pulmonary Circulation
EditorsJ.X.J Yuan, J.P.T. Ward
Pages419-434
Number of pages16
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
Volume661
ISSN (Print)0065-2598

Keywords

  • Caldesmon
  • Cytoskeleton
  • Endothelium
  • Sorafenib
  • Vascular remodeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Moreno-Vinasco, L., & Garcia, J. G. N. (2010). Receptor tyrosine kinase inhibitors in rodent pulmonary hypertension. In J. X. J. Yuan, & J. P. T. Ward (Eds.), Membrane Receptors, Channels and Transporters in Pulmonary Circulation (pp. 419-434). (Advances in Experimental Medicine and Biology; Vol. 661). https://doi.org/10.1007/978-1-60761-500-2_27