What is the clinical evidence from this study?

Study design: Other. Intervention: Recombinant human erythropoietin (rhEPO) and VEGF vs. Each agent alone or control. Primary outcome: Endothelial cell proliferation and cytosolic Ca2+ mobilization (p=<0.01).

November 1, 1998Journal of the American Society of Nephrology

Role of vascular endothelial growth factor on erythropoietin-related endothelial cell proliferation.

Q: What are the key findings of this study?

Recombinant human erythropoietin and VEGF synergistically promote endothelial cell proliferation and upregulate VEGF receptors KDR/flk-1 and flt-1 in bovine aorta endothelial cells.

Q: What question did this study set out to answer?

To determine the molecular mechanisms through which recombinant human erythropoietin promotes endothelial cell proliferation and to evaluate its functional interaction with vascular endothelial growth factor.

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Key result

Recombinant human erythropoietin and VEGF synergistically promote endothelial cell proliferation and upregulate VEGF receptors KDR/flk-1 and flt-1 in bovine aorta endothelial cells.

Population

Endothelial cells from bovine aorta (BAEC)

Comparison

Recombinant human erythropoietin with or without… vs Control conditions

Design

Preclinical

Authors

MAM V Alvarez ArroyoHospital Clínico San Carlos MCMaría Ángeles CastillaInstituto de Biomedicina de Sevilla FPFrancisco Román González PachecoHospital Universitario Fundación Jiménez Díaz

Discussion

Member takes

Implication

Preclinical EPO-VEGF synergy in bovine cells warrants no clinical extrapolation; leaves open in vivo and human validation of angiogenic effects.

Key Points

To determine the molecular mechanisms through which recombinant human erythropoietin promotes endothelial cell proliferation and to evaluate its functional interaction with vascular endothelial growth factor.
Cultured bovine aortic endothelial cells were exposed to recombinant human erythropoietin, vascular endothelial growth factor, or fetal calf serum alone and in combination.
Assessed proliferation inhibition via anti-VEGF neutralizing antibodies, measured cytosolic calcium mobilization, and evaluated mRNA expression of VEGF receptors (KDR/flk-1 and flt-1) in the presence or absence of genistein.
An anti-VEGF antibody blocked erythropoietin-induced cell proliferation by 92.8 ± 2.2% (P < 0.01), and co-treatment of erythropoietin (20 U/ml) and VEGF (5 x 10^-11 M) increased cell count by 117.8 ± 6.9% compared to 0.3 ± 2.8% for erythropoietin alone and 52.9 ± 3.1% for VEGF alone (P < 0.01).
Erythropoietin pretreatment significantly amplified VEGF-stimulated cytosolic calcium mobilization (Δ[Ca2+]i = 704 ± 111 nM vs 246 ± 36 nM in untreated controls, P < 0.01).
Erythropoietin upregulated mRNA expression of both VEGF receptors KDR/flk-1 and flt-1, a response mediated by tyrosine phosphorylation and inhibited by genistein.

Structured PICO

Population

Endothelial cells from bovine aorta (BAEC)

Intervention

Recombinant human erythropoietin (rhEPO) (e.g., 20 U/ml) with or without vascular endothelial growth factor (VEGF)

Comparator

Control conditions (absence of rhEPO, absence of VEGF, or each agent alone)

Outcome

Endothelial cell proliferation and mechanisms of action (cytosolic Ca2+ mobilization, mRNA expression of VEGF receptors KDR/flk-1 and flt-1)surrogate

Main Result

p-value: p=<0.01

Recombinant human erythropoietin promotes endothelial cell proliferation by upregulating VEGF receptors and enhancing VEGF-mediated effects, suggesting a mechanism for its role in neovascularization.

Cite This Study

Arroyo et al. (1998) studied this question. Recombinant human erythropoietin (rhEPO) and VEGF vs. Each agent alone or control was evaluated on Endothelial cell proliferation and cytosolic Ca2+ mobilization (p=<0.01). Recombinant human erythropoietin and VEGF synergistically promote endothelial cell proliferation and upregulate VEGF receptors KDR/flk-1 and flt-1 in bovine aorta endothelial cells.

synapsesocial.com/papers/6a917e6449be6cf6a84676db https://doi.org/10.1681/asn.v9111998

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Implication

Preclinical EPO-VEGF synergy in bovine cells warrants no clinical extrapolation; leaves open in vivo and human validation of angiogenic effects.

Role of vascular endothelial growth factor on erythropoietin-related endothelial cell proliferation.

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Role of vascular endothelial growth factor on erythropoietin-related endothelial cell proliferation.

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

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Also Consider