Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells

• Autorzy: Jozkowicz A. , Pankiewicz J. , Dulak J. , Partyka L. , Wybranska I. , Huk I. , Dembinska-Kiec A.
• Języki publikacji: EN

Abstrakty

EN

The regulation of vascular wall homeostasis by nitric oxide (NO) generated by endothelium is being intensively studied. In the present paper, the involvement of NO in the vascular endothelial growth factor (VEGF), insulin or leptin-stimulated proliferation of human endothelial cells (HUVEC) was measured by [3H]thymidine or bromodeoxyuridine incorporation. VEGF and insulin, but not leptin, increased NO generation in HUVEC, as detected with ISO-NO electrode. Proliferation of HUVEC induced by leptin was not changed or was higher in the presence of L-Nω-nitro-L-arginine methyl ester (L-NAME) a nitric oxide synthase (NOS) inhibitor. In contrast, L-NAME blunted the proproliferative effect of VEGF and insulin. Furthermore, we demonstrated that, in human arterial smooth muscle cells (hASMC) transfected with endothelial NOS (eNOS) gene, the generation of biologically active VEGF protein was NO-dependent. Inhibition of NO generation by L-NAME decreased the synthesis of VEGF protein and attenuated HUVEC proliferation induced by conditioned media from transfected hASMC. Endothelium-derived NO seems to participate in VEGF and insulin, but not leptin, mitogenic activity. Additionally, the small amounts of NO released from endothelial cells, as mimicked by eNOS transfection into hASMC, may activate generation of VEGF in sub-endothelial smooth muscle cells, leading to increased synthesis of VEGF protein necessary for turnover and restitution of endothelial cells.

Słowa kluczowe

EN

leptin; nitric oxide synthase; cell; insulin; vascular wall; homeostasis; proliferation; vascular smooth muscle; nitric oxide; transfection; endothelium; inhibitor; vascular endothelial growth factor

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1999
• Tom: 46
• Numer: 3
• Opis fizyczny: p.703-715,fig.

Twórcy

autor

Jozkowicz A.

• Jagiellonian University School of Medicine, M.Kopernika 15a, 31-501 Krakow, Poland

autor

Pankiewicz J.

autor

Dulak J.

autor

Partyka L.

autor

Wybranska I.

autor

Huk I.

autor

Dembinska-Kiec A.

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