High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension

Nambirajan Sundaram, Anitaben Tailor, Laurel Mendelsohn, Janaka Wansapura, Xunde Wang, Tomoyasu Higashimoto, Michael W. Pauciulo, William Gottliebson, Vijay K. Kalra, William C. Nichols, Gregory J. Kato, Punam Malik

Research output: Contribution to journalArticle

Abstract

Pulmonary hypertension is associated with reduced nitric oxide bioavailability and early mortality in sickle cell disease (SCD). We previously demonstrated that placenta growth factor (PlGF), an angiogenic factor produced by erythroid cells, induces hypoxia-independent expression of the pulmonary vasoconstrictor endothelin-1 in pulmonary endothelial cells. Using a lentivirus vector, we simulated erythroid expression of PlGF in normal mice up to the levels seen in sickle mice. Consequently, endothelin-1 production increased, right ventricle pressures increased, and right ventricle hypertrophy and pulmonary changes occurred in the mice within 8 weeks. These findings were corroborated in 123 patients with SCD, inwhom plasma PlGF levels were significantly associated with anemia, endothelin-1, and tricuspid regurgitant velocity; the latter is reflective of peak pulmonary artery pressure. These results illuminate a novel mechanistic pathway linking hemolysis and erythroid hyperplasia to increased PlGF, endothelin-1, and pulmonary hypertension in SCD, and suggest that strategies that block PlGF signaling may be therapeutically beneficial. This trial was registered at http://clinicaltrials.gov as #NCT00011648.

Original languageEnglish (US)
Pages (from-to)109-112
Number of pages4
JournalBlood
Volume116
Issue number1
DOIs
StatePublished - Jul 8 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Sundaram, N., Tailor, A., Mendelsohn, L., Wansapura, J., Wang, X., Higashimoto, T., Pauciulo, M. W., Gottliebson, W., Kalra, V. K., Nichols, W. C., Kato, G. J., & Malik, P. (2010). High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood, 116(1), 109-112. https://doi.org/10.1182/blood-2009-09-244830