1. Beneficial role of the phytoestrogen genistein on vascular calcification.
- Author
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Cepeda SB, Sandoval MJ, Rauschemberger MB, and Massheimer VL
- Subjects
- Animals, Animals, Newborn, Aorta, Biomarkers metabolism, Cell Movement, Cell Proliferation, Cell Transdifferentiation, Cells, Cultured, Dietary Supplements, Endothelium, Vascular cytology, Endothelium, Vascular immunology, Endothelium, Vascular pathology, Female, Genistein therapeutic use, Intercellular Adhesion Molecule-1 chemistry, Intercellular Adhesion Molecule-1 genetics, Intercellular Adhesion Molecule-1 metabolism, Monocytes cytology, Monocytes immunology, Monocytes pathology, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular immunology, Muscle, Smooth, Vascular pathology, Osteoblasts cytology, Osteoblasts immunology, Osteoblasts metabolism, Osteoblasts pathology, Osteogenesis, Phytoestrogens therapeutic use, Rats, Wistar, Skull, Vascular Calcification immunology, Vascular Calcification metabolism, Vascular Calcification pathology, Endothelium, Vascular metabolism, Gene Expression Regulation, Genistein metabolism, Monocytes metabolism, Muscle, Smooth, Vascular metabolism, Phytoestrogens metabolism, Vascular Calcification prevention & control
- Abstract
Although soy phytoestrogen are proposed to prevent or improve postmenopausal vascular and bone diseases, the currently available data are controversial and unclear. In this study we evaluated the molecular and biochemical action of genistein on the cellular events involved in vascular calcification. Rat monocytes, aortic vascular cell and osteoblasts cultures in vitro exposed to Gen were employed. Gen down regulated the expression of cell adhesion molecules involved in stable leukocyte attachment. Using flow cytometry we found that the PE significantly diminished monocyte integrins CD11b, CD11c and CD18 expression either under basal and pro-inflammatory environment. At endothelial level, Gen also reduced Intercellular Adhesion Molecule 1 mRNA expression. On vascular muscle cells, the PE markedly reduced cell proliferation and migration. When vascular calcification was studied, muscle cells transdifferentiation into osteoblasts like cells was evaluated. Cells were cultured in osteogenic medium for 21 days. The expression of alkaline phosphatase and the presence of calcified nodules in the extracellular matrix were selected as features of muscle transdifferentiation. Calcified muscle cells exhibited higher levels of alkaline phosphatase activity and enhanced deposition of calcium nodules respect to native cells. Both osteoblastic markers were significantly reduced after Gen treatment. In contrast to this anti-osteogenic action, on bone cells Gen promoted osteoblasts growth, enhanced alkaline phosphatase activity and increased matrix mineralization. Its mitogenic action on osteoblasts directly depends on nitric oxide endothelial production stimulated by the PE. The data presented suppose a beneficial role of Gen on bone and vascular cells, with a cross link between both systems., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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