کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473672 | 1550407 | 2016 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sustained activation of ADP/P2ry12 signaling induces SMC senescence contributing to thoracic aortic aneurysm/dissection
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کلمات کلیدی
P2RY12SMCsBAPNSAACXCL1SA-β-galHMGB1ADPHspSASPMMP-9TAADSMCDAMPsECMROS - ROSsenescence-associated β-galactosidase - β-گالاکتوزیداز وابسته به پیریAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPadenosine diphosphate - آدنوزین دی فسفاتER stress - استرس استEndoplasmic reticulum stress - استرس شبکه آندوپلاسمیdamage-associated molecular patterns - الگوهای مولکولی مرتبط با آسیبtumor necrosis factor-α - تومور نکروز عامل αserum amyloid A - سرم آمیلوئید ASmooth muscle cell - سلول عضلانی صافTNF-α - فاکتور نکروز توموری آلفاSenescence-associated secretory phenotype - فنوتیپ ترشحی مرتبط با سن زاییExtracellular matrix - ماتریکس خارج سلولیMatrix metalloproteinase 9 - ماتریکس متالوپروتئیناز 9High-mobility group box 1 protein - پروتئین جعبه 1 پروتئین گروه تحریر بالاHeat shock protein - پروتئین شوک حرارتSenescence - پیریReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Thoracic aortic aneurysm/dissection (TAAD) is characterized by excessive smooth muscle cell (SMC) loss, extracellular matrix (ECM) degradation and inflammation. However, the mechanism whereby signaling leads to SMC loss is unclear. We used senescence-associated (SA)-β-gal staining and analysis of expression of senescence-related proteins (p53, p21, p19) to show that excessive mechanical stretch (20% elongation, 3600 cycles/h, 48 h) induced SMC senescence. SMC senescence was also detected in TAAD specimens from both mice and humans. High-performance liquid chromatography and luciferin-luciferase-based assay revealed that excessive mechanical stretch increased adenosine diphosphate (ADP) release from SMCs both in vivo and in vitro. Elevated ADP induced SMC senescence while genetic knockout of the ADP receptor, P2Y G protein-coupled receptor 12 (P2ry12), in mice protected against SMC senescence and inflammation. Both TAAD formation and rupture were significantly reduced in P2ry12â/â mice. SMCs from P2ry12â/â mice were resistant to senescence induced by excessive mechanical stretch or ADP treatment. Mechanistically, ADP treatment sustained Ras activation, whereas pharmacological inhibition of Ras protected against SMC senescence and reduced TAAD formation. Taken together, excessive mechanical stress may induce a sustained release of ADP and promote SMC senescence via P2ry12-dependent sustained Ras activation, thereby contributing to excessive inflammation and degeneration, which provides insights into TAAD formation and progression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 99, October 2016, Pages 76-86
Journal: Journal of Molecular and Cellular Cardiology - Volume 99, October 2016, Pages 76-86
نویسندگان
Wen-Mei Zhang, Yan Liu, Tao-Tao Li, Chun-Mei Piao, Ou Liu, Jun-Ling Liu, Yong-Fen Qi, Li-Xin Jia, Jie Du,