Shear Stress Induces Nitric Oxide-Mediated Vascular Endothelial Growth Factor Production in Human Adipose Tissue Mesenchymal Stem Cells

Author(s)

Bassaneze, Vinicius ; Barauna, Valerio Garrone ; Lavini-Ramos, Carolina ; Kalil, Jorge ; Schettert, Isolmar Tadeu ; Miyakawa, Ayumi Aurea ; Krieger, Jose Eduardo ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Inst Heart InCor, Lab Genet & Mol Cardiol, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: STEM CELLS AND DEVELOPMENT; v. 19, n. 3, p. 371-378, MAR 2010.
• Web of Science Citations: 43

Abstract

It has been demonstrated that human adipose tissue-derived mesenchymal stem cells (hASCs) enhance vascular density in ischemic tissues, suggesting that they can differentiate into vascular cells or release angiogenic factors that may stimulate neoangiogenesis. Moreover, there is evidence that shear stress (SS) may activate proliferation and differentiation of embryonic and endothelial precursor stem cells into endothelial cells (ECs). In this work, we investigated the effect of laminar SS in promoting differentiation of hASCs into ECs. SS (10 dyn/cm(2) up to 96 h), produced by a cone plate system, failed to induce EC markers (CD31, vWF, Flk-1) on hASC assayed by RT-PCR and flow cytometry. In contrast, there was a cumulative production of nitric oxide (determined by Griess Reaction) and vascular endothelial growth factor (VEGF; by ELISA) up to 96 h of SS stimulation ( NO(2)(-) in nmol/10(4) cells: static: 0.20 +/- 0.03; SS: 1.78 +/- 0.38, n = 6; VEGF in pg/10(4) cells: static: 191.31 +/- v35.29; SS: 372.80 +/- 46.74, n = 6, P < 0.05). Interestingly, the VEGF production was abrogated by 5 mM N(G)-L-nitro-arginine methyl ester (L-NAME) treatment (VEGF in pg/10(4) cells: SS: 378.80 +/- 46.74, n = 6; SS + L-NAME: 205.84 +/- 91.66, n = 4, P < 0.05). The results indicate that even though SS failed to induce EC surface markers in hASC under the tested conditions, it stimulated NO-dependent VEGF production. (AU)

• FAPESP's process: 07/58942-0 - From the bench to clinical trials: development of biomarkers as response predictors to therapy and target organs damage in systemic arterial hypertension
• Grantee: Eduardo Moacyr Krieger
• Support Opportunities: Research Projects - Thematic Grants