IMPAM   23988
INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
artículos
Título:
Macrophages derived from septic mice modulate nitric oxide synthase and angiogenic mediators in the heart
Autor/es:
EULALIA DE LA TORRE; HOVSEPIAN EUGENIA; PENAS FEDERICO; DMYTRENKO GANNA ; CASTRO E. MARÍA; GOREN NORA BEATRIZ; SALES MARÍA ELENA
Revista:
JOURNAL OF CELLULAR PHYSIOLOGY
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2013 vol. 228 p. 1584 - 1584
ISSN:
0021-9541
Resumen:
Macrophages (Mps) can exert the defense against invading pathogens. During sepsis, bacterial lipopolisaccharide (LPS) activates the production of inflammatory mediators by Mps. Nitric oxide synthase (NOS) derived-nitric oxide (NO) is one of them. Besides, Mps may produce pro-angiogenic molecules such as vascular endothelial growth factor-A (VEGF-A) and metalloproteinases (MMPs). The mechanisms involved in the cardiac neovascular response by Mps during sepsis are not completely known. We investigated the ability of LPS-treated Mps from septic mice to modulate the behavior of cardiac cells as producers of NO and angiogenic molecules. In vivo LPS treatment (0.1 mg/mouse) increased NO production more than fourfold and induced de novo NOS2 expression in Mps. Immunoblotting assays also showed an induction in VEGF-A and MMP-9 expression in lysates obtained from LPS-treated Mps, and MMP-9 activity was detected by zymography in cell supernatants. LPS-activated Mps co-cultured with normal heart induced the expression of CD31 and VEGF-A in heart homogenates and increased MMP-9 activity in the supernatants. By immunohistochemistry, we detected new blood vessel formation in hearts cultured with LPS treated Mps. When LPS-stimulated Mps were co-cultured with isolated cardiomyocytes in a transwell assay, the expression of NOS2, VEGF-A and MMP-9 was induced in cardiac cells. In addition, MMP-9 activity was up-regulated in the supernatant of cardiomyocytes. The latter was due to NOS2 induction in Mps from in vivo LPS-treated mice. In conclusion LPS-treated Mps are inducers of inflammatory/angiogenic mediators in cardiac cells, which could be triggering neovascularization, as an attempt to improve cardiac performance in sepsis.
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