التفاصيل البيبلوغرافية
| العنوان: |
Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous |
| المؤلفون: |
Frédéric Perros, Pierre Sentenac, David Boulate, Grégoire Manaud, Tom Kotsimbos, Florence Lecerf, Lilia Lamrani, Elie Fadel, Olaf Mercier, Arturo Londono-Vallejo, Marc Humbert, Saadia Eddahibi |
| المصدر: |
International Journal of Molecular Sciences; Volume 20; Issue 14; Pages: 3575 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2019 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
idiopathic pulmonary artery hypertension, pulmonary artery smooth muscle cells, proliferation, energetic metabolism, DNA damage |
| جغرافية الموضوع: |
agris |
| الوصف: |
Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage/repair factors (γH2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells—the defining feature of neoplasia. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Biology; https://dx.doi.org/10.3390/ijms20143575 |
| DOI: |
10.3390/ijms20143575 |
| الاتاحة: |
https://doi.org/10.3390/ijms20143575 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.21C4B321 |
| قاعدة البيانات: |
BASE |