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Investigation of the molecular mechanisms inducing vascular damage in systemic sclerosis

Duong, Thi Bich Thuan (2016) Investigation of the molecular mechanisms inducing vascular damage in systemic sclerosis. Doctoral Thesis.

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Abstract

Purposes - This study was conducted to investigate whether oxidative stress and Endothelial-to-Mesenchymal Transition (EndMT) may be part of the molecular machinery inducing vascular damage in systemic sclerosis (SSc). The possibility that iloprost, a drug commonly used in SSc therapy, might modulate the above-mentioned biological phenomena was also investigated.
Results - Sera from SSc patients markedly increased ROS levels, proliferation, and collagen synthesis in human pulmonary microvascular endothelial cells (HPMECs). Interestingly, SSc sera taken after 5 hours of iloprost infusion could attenuate ROS levels and collagen synthesis.
Preliminary results show that SSc sera induced the conversion of ECs into myofibroblasts through decreasing the endothelial marker, von Willebrand Factor, and increasing α-smooth muscle actin, the myofibroblastic marker.
Conclusion - Exposition of HPMECs to pro-oxidant factors present in SSc sera increased disease-associated physio-pathological phenomena such as intracellular ROS levels and collagen synthesis. Reduction of the above-mentioned phenomena by iloprost suggests a potential antioxidant effect of this drug. Preliminary data demonstrate the presence of an SSc sera-induced EndMT, indicating this phenotypic shift as an important etiological mechanism of SSc-associated vascular damage and a potential therapeutic target to inhibit obliterative vascular disorder and tissue fibrosis.

Item Type:Doctoral Thesis
ID Code:11116
Contributors:Pintus, Gianfranco and Huynh, Dinh Chien
Publisher:Universita' degli studi di Sassari
Uncontrolled Keywords:Systemic sclerosis, oxidative stress, ROS, EndMT, iloprost
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Cicli, scuole e corsi:Ciclo 28 > Scienze biomolecolari e biotecnologiche > Biochimica, fisiologia e biologia molecolare
Deposited On:02 May 2016 18:26

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