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Cellular and molecular study of vascular damage during systemic sclerosis

Totiger, Tulasigeri Malapa (2015) Cellular and molecular study of vascular damage during systemic sclerosis. Doctoral Thesis.

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Abstract

Systemic Sclerosis is a devastating vascular, connective and a multisystem autoimmune disease characterized by fibrosis of skin and internal organs. Pulmonary arterial hypertension (PAH) is one of the clinical manifestations of SSc that arise as a result of cellular and molecular vascular damage in the vascular wall. Oxidative stress is largely evidenced in the development of arterial hypertension in SSc. And, it is likely that circulating pro-oxidant factors may be involved in the pathogenesis of SSc-PAH by inducing VSMCs activation and phenotypic switch. So we speculate, that in SSc patients associated with Pulmonary Arterial Hypertension (PAH), circulating factors may drive an aberrant vascular remodeling by exerting pro-oxidant and pro-fibrotic effects on Human Pulmonary Arterial Smooth Muscle Cells (HPASMCs) and activate collagen I synthesis. To test this hypothesis, we exposed primary Human Pulmonary Artery Smooth Muscle Cells (HPASMCs) to serum obtained from SSc patients with or without PAH and healthy donors (HD) and looked for the production of reactive oxygen species (ROS) and collagen I synthesis. From our study, we found that SSc-PAH patients’ circulating factors exhibited pro-oxidant effect by inducing ROS generation through NOX2 in HPASMCs and we also found that, circulating factors exhibited pro-fibrotic effect by inducing activation of collagen I synthesis in HPASMCs via ERK signaling, thus asserting the vascular damage in SSc patients.

Item Type:Doctoral Thesis
ID Code:10627
Contributors:Pintus, Gianfranco
Publisher:Università degli studi di Sassari
Uncontrolled Keywords:Vascular damage, Oxidative stress, SSc-PAH
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 27 > Biomolecular and Biotechnological Sciences > Biochimica, Fisiologia e Biologia molecolare
Deposited On:18 Mar 2015 13:06

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