Homocysteinylated albumin promotes increased monocyte-endothelial cell adhesion and up-regulation of MCP1, Hsp60 and ADAM17
| العنوان: | Homocysteinylated albumin promotes increased monocyte-endothelial cell adhesion and up-regulation of MCP1, Hsp60 and ADAM17 |
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| المؤلفون: | Amelia Cimmino, Cinzia Lombardi, Filomena Acanfora, Diego Ingrosso, Sofia Salemme, Rosanna Capasso, Donald L. Puppione, Ersilia Satta, Alessandra F. Perna, Irene Sambri |
| المساهمون: | Capasso, Rosanna, Sambri, Irene, Cimmino, Amelia, Salemme, Sofia, Lombardi, Cinzia, Acanfora, Filomena, Satta, Ersilia, Puppione, Dl, Perna, Alessandra, Ingrosso, Diego |
| المصدر: | PLoS ONE, Vol 7, Iss 2, p e31388 (2012) PLoS ONE |
| بيانات النشر: | Public Library of Science, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | CCR2, Chemokine, Science, Population, Serum albumin, 030204 cardiovascular system & hematology, ADAM17 Protein, Cardiovascular, Biochemistry, Monocytes, Cell Line, Molecular Genetics, 03 medical and health sciences, 0302 clinical medicine, Albumins, Molecular Cell Biology, Genetics, medicine, Cell Adhesion, Humans, Cell adhesion, education, Biology, Homocysteine, Chemokine CCL2, 030304 developmental biology, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Monocyte, Albumin, Endothelial Cells, Chaperonin 60, Molecular biology, Cell biology, Up-Regulation, Endothelial stem cell, ADAM Proteins, medicine.anatomical_structure, Nephrology, biology.protein, Medicine, Research Article |
| الوصف: | The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE: Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS: Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS: Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling. Rationale: The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. Objective: Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. Methods and Results: Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. Conclusions: Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling. © 2012 Capasso et al. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a421c7f4f71b87e1003c250350090d5Test http://hdl.handle.net/11591/231436Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6a421c7f4f71b87e1003c250350090d5 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |