| Autor: |
Sonja Suvakov, Hajrunisa Cubro, Wendy M. White, Yvonne S. Butler Tobah, Tracey L. Weissgerber, Kyra L. Jordan, Xiang Y. Zhu, John R. Woollard, Fouad T. Chebib, Natasa M. Milic, Joseph P. Grande, Ming Xu, Tamara Tchkonia, James L. Kirkland, Lilach O. Lerman, Vesna D. Garovic |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Biology of Sex Differences, Vol 10, Iss 1, Pp 1-13 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2042-6410 |
| DOI: |
10.1186/s13293-019-0263-5 |
| Popis: |
Abstract Background Preeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia. Methods MSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC, n = 10) and those with normotensive pregnancies (NP-MSC, n = 12). Sections of the frozen subcutaneous adipose tissue were assessed for inflammation by staining for tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1. Viability, proliferation, and migration were compared between PE-MSC vs. NP-MSC. Apoptosis and angiogenesis were assayed before and after treatment with a senolytic agent (1 μM dasatinib) using the IncuCyte S3 Live-Cell Analysis System. Similarly, staining for senescence-associated beta galactosidase (SABG) and qPCR for gene expression of senescence markers, p16 and p21, as well as senescence-associated secretory phenotype (SASP) components, IL-6, IL-8, MCP-1, and PAI-1, were studied before and after treatment with dasatinib and compared between PE and NP. Results After in vitro exposure to TNF-alpha, MSC demonstrated upregulation of SASP components, including interleukins-6 and -8 and MCP-1. Staining of the subcutaneous adipose tissue sections revealed a greater inflammatory response in preeclampsia, based on the higher levels of both TNF-alpha and MCP-1 compared to normotensive pregnancies (p |
| Databáze: |
Directory of Open Access Journals |
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