Ceramide mediates Ox-LDL-induced human vascular smooth muscle cell calcification via p38 mitogen-activated protein kinase signaling
| العنوان: | Ceramide mediates Ox-LDL-induced human vascular smooth muscle cell calcification via p38 mitogen-activated protein kinase signaling |
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| المؤلفون: | Yan Song, Qin Zhou, Lizhen Liao, Huimin Yu, Wei-Kang Wu, Yanling Chen, Lihe Lu, Meihong Ye, Sheng Wang |
| المصدر: | PLoS ONE, Vol 8, Iss 12, p e82379 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | MAPK/ERK pathway, medicine.medical_specialty, Ceramide, Vascular smooth muscle, p38 mitogen-activated protein kinases, Myocytes, Smooth Muscle, lcsh:Medicine, Apoptosis, Sphingomyelin phosphodiesterase, Biology, Ceramides, Benzylidene Compounds, p38 Mitogen-Activated Protein Kinases, Muscle, Smooth, Vascular, chemistry.chemical_compound, Internal medicine, medicine, Humans, Phosphorylation, Protein kinase A, Vascular Calcification, lcsh:Science, Cells, Cultured, Multidisciplinary, Aniline Compounds, lcsh:R, medicine.disease, musculoskeletal system, Cell biology, Femoral Artery, Lipoproteins, LDL, Endocrinology, Sphingomyelin Phosphodiesterase, chemistry, cardiovascular system, lipids (amino acids, peptides, and proteins), lcsh:Q, Signal transduction, Calcification, Research Article, Signal Transduction |
| الوصف: | Vascular calcification is associated with significant cardiovascular morbidity and mortality, and has been demonstrated as an actively regulated process resembling bone formation. Oxidized low density lipoprotein (Ox-LDL) has been identified as a regulatory factor involved in calcification of vascular smooth muscle cells (VSMCs). Additionally, over-expression of recombinant human neutral sphingomyelinase (N-SMase) has been shown to stimulate VSMC apoptosis, which plays an important role in the progression of vascular calcification. The aim of this study is to investigate whether ceramide regulates Ox-LDL-induced calcification of VSMCs via activation of p38 mitogen-activated protein kinase (MAPK) pathway. Ox-LDL increased the activity of N-SMase and the level of ceramide in cultured VSMCs. Calcification and the osteogenic transcription factor, Msx2 mRNA expression were reduced by N-SMase inhibitor, GW4869 in the presence of Ox-LDL. Usage of GW4869 inhibited Ox-LDL-induced apoptosis in VSMCs, an effect which was reversed by C2-ceramide. Additionally, C2-ceramide treatment accelerated VSMC calcification, with a concomitant increase in ALP activity. Furthermore, C2-ceramide treatment enhanced Ox-LDL-induced VSMC calcification. Addition of caspase inhibitor, ZVAD-fmk attenuated Ox-LDL-induced calcification. Both Ox-LDL and C2-ceramide treatment increased the phosphorylation of p38 MAPK. Inhibition of p38 MAPK by SB203580 attenuated Ox-LDL-induced calcification of VSMCs. These data suggest that Ox-LDL activates N-SMase-ceramide signaling pathway, and stimulates phosphorylation of p38 MAPK, leading to apoptosis in VSMCs, which initiates VSMC calcification. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed31ccb8ca2b5a3027f68d9b3c788f2a http://europepmc.org/articles/PMC3865066?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ed31ccb8ca2b5a3027f68d9b3c788f2a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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