Angiotensin-(1-7) synergizes with colony-stimulating factors in hematopoietic recovery

Kathleen E. Rodgers, Theresa B. Espinoza, Norma Roda, Christopher J. Meeks, Gere S. Dizerega

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Purpose: Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and the recovery of circulating formed elements following chemotherapy. Methods: Mice were injected with gemcitabine followed 2 days later with A(1-7). Circulating blood cells and bone marrow progenitors were measured over time. Results: Combination of A(1-7) with Neupogen (the latter given only 3 days starting at the white blood cell nadir) decreased the amount of Neupogen needed for optimal recovery by 10-fold. The progenitors measured include CFU-GEMM, CFU-GM, CFU-Meg and BFU-E. A(1-7) increased recovery of all progenitors when given alone or in combination with Neupogen above that with Neupogen alone. Combination of A(1-7) with Epogen slightly increased (not significantly) red blood cell concentrations above those achieved by Epogen alone. However, in this model, A(1-7) or A(1-7) in combination with Epogen increased all erythroid progenitors with the largest effect on early erythroid progenitors (immature BFU-E). Conclusions: Neupogen and Epogen acted synergistically with A(1-7) to increase the concentration of myeloid, megakaryocytic and erythroid progenitor cells in the bone marrow following chemotherapy suggesting that A(1-7)'s multilineage effect on early progenitors in the marrow facilitates proliferation in response to lineage-specific growth factors.

Original languageEnglish (US)
Pages (from-to)1235-1245
Number of pages11
JournalCancer Chemotherapy And Pharmacology
Volume72
Issue number6
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • Angiotensin 1-7
  • Bone marrow recovery
  • Chemotherapy
  • Colony-stimulating factor

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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