دورية أكاديمية
The Role of Nitric Oxide and Cyclic Guanosine Monophosphate Signaling in Arteriovenous Fistula Maturation
| العنوان: | The Role of Nitric Oxide and Cyclic Guanosine Monophosphate Signaling in Arteriovenous Fistula Maturation |
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| المؤلفون: | Somarathna, Maheshika S |
| المصدر: | All ETDs from UAB |
| بيانات النشر: | UAB Digital Commons |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Arteriovenous fistula, Maturation failure, Nitric oxide, Cyclic guanosine monophosphate, Intimal hyperplasia, Vascular outward remodeling, Doctor of Philosophy (PhD) Heersink School of Medicine, Medical Sciences |
| الوصف: | Vascular access is the single most important component of the hemodialysis procedure and the arteriovenous fistula (AVF) is the most preferred type. However, 60% of AVFs created fail to mature successfully for dialysis use (AVF maturation failure). AVF maturation failure is primarily the result of 1) intimal hyperplasia formation (IH) and 2) poor vascular outward remodeling. Currently, a major unmet clinical need in the field is the lack of effective therapies to treat/prevent AVF maturation failure due to the poor understanding of molecular mechanisms. This proposal is designed to: 1) elucidate the pathologic significance of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling pathway on AVF maturation, 2) evaluate novel therapies/strategies to promote AVF maturation and 3) characterize rodent animal models important to elucidate mechanisms of vascular remodeling following vascular injury. AVF creation resulted in endothelial dysfunction in early time points and smooth muscle cell dysfunction in the later time point which accompanied by dysregulation of mediators that regulate NOS3 function and cGMP levels. By utilizing genetically modified mouse models we demonstrated that NO is critical for inhibition of IH and to promote vascular outward remodeling and hemodynamics following AVF creation which supported the rationale to provide NO as a therapy. Consequently, we demonstrate that perivascular delivery of novel NO releasing nanomatrix gel therapy can promote AVF maturation. iv Furthermore, we demonstrated that phosphodiesterase-5A (PDE5A-which degrade cGMP) expression is significantly increased following AVF creation and identified PDE5A as a drug target to modulate cGMP signaling. Consequently, inhibition of PDE5A with sildenafil resulted in increased blood flow and the outward expansion in AVF veins without affecting the level of intimal hyperplasia suggesting sildenafil treatment can promote AVF maturation by enhancing vascular outward remodeling. Finally, by utilizing a rat balloon ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.library.uab.edu/etd-collection/337Test; https://digitalcommons.library.uab.edu/context/etd-collection/article/1328/viewcontent/Somarathna_uab_0005D_13294.pdfTest |
| الإتاحة: | https://digitalcommons.library.uab.edu/etd-collection/337Test https://digitalcommons.library.uab.edu/context/etd-collection/article/1328/viewcontent/Somarathna_uab_0005D_13294.pdfTest |
| رقم الانضمام: | edsbas.3DF28A8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |