التفاصيل البيبلوغرافية
| العنوان: |
Hypoxia and hypoxia‐inducible factors promote the development of neointimal hyperplasia in arteriovenous fistula |
| المؤلفون: |
Sadaghianloo, Nirvana, Contenti, Julie, Declemy, Serge, Ambrosetti, Damien, Zdralevic, Masa, Tannour‐Louet, Mounia, Fabbri, Lucilla, Pagès, Gilles, Bost, Frédéric, Hassen‐Khodja, Réda, Pouysségur, Jacques, Jean‐Baptiste, Elixène, Dardik, Alan, Mazure, Nathalie M. |
| المصدر: |
The Journal of Physiology ; volume 599, issue 8, page 2299-2321 ; ISSN 0022-3751 1469-7793 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2021 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Key points Patients with end‐stage renal failure need arteriovenous fistulas (AVF) to undergo dialysis. However, AVFs present a high rate of failure as a result of excessive venous thickness. Excessive venous thickness may be a consequence of surgical dissection and change in oxygen concentration within the venous wall. We show that venous cells adapt their metabolism and growth depending on oxygen concentration, and drugs targeting the hypoxic response pathway modulate this response in vitro . We used the same drugs on a mouse model of AVF and show that direct or indirect inhibition of the hypoxia‐inducible factors (HIFs) help decrease excessive venous thickness. Hypoxia and HIFs can be targets of therapeutic drugs to prevent excessive venous thickness in patients undergoing AVF surgical creation. Abstract Because the oxygen concentration changes in the venous wall, surrounding tissue and the blood during surgical creation of arteriovenous fistula (AVF), we hypothesized that hypoxia could contribute to AVF failure as a result of neointimal hyperplasia. We postulated that modulation of the hypoxia‐inducible factors (HIF) with pharmacological compounds could promote AVF maturation. Fibroblasts [normal human fibroblasts (NHF)], smooth muscle cells [human umbilical vein smooth muscle cells (HUVSMC)] and endothelial cells [human umbilical vein endothelial cells (HUVEC)], representing the three layers of the venous wall, were tested in vitro for proliferation, cell death, metabolism, reactive oxygen species production and migration after silencing of HIF1/2‐α or after treatment with deferioxamine (DFO), everolimus (Eve), metformin (Met), N ‐acetyl‐ l ‐cysteine (NAC) and topoisomerase I (TOPO), which modulate HIF‐α stability or activity. Compounds that were considered to most probably modify intimal hyperplasia were applied locally to the vessels in a mouse model of aortocaval fistula. We showed, in vitro , that NHF and HUVSMC can adapt their metabolism and thus their growth depending on oxygen concentration, whereas ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1113/jp281218 |
| DOI: |
10.1113/JP281218 |
| الإتاحة: |
https://doi.org/10.1113/jp281218Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.FC5FC05 |
| قاعدة البيانات: |
BASE |
