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Role of the SphK1/S1P Signaling Axis in the Pathogenesis of Pulmonary Arterial Hypertension

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posted on 25.07.2018 by Justin Sysol
Pulmonary arterial hypertension (PAH) is a severe, progressive and fatal disease for which there is currently no curative treatment available. Pathologic changes in this disease involve remodeling of the pulmonary vasculature, including marked proliferation of smooth muscle and endothelial cells, leading to occlusion of vessels via poorly understood mechanisms. This remodeling causes increased pulmonary vascular resistance (PVR) and subsequent pulmonary artery pressure, ultimately leading to right heart failure due to pressure overload, a major cause of death. Despite active research in PAH pathobiology, therapies to hinder or reverse the pathologic vascular remodeling in this debilitating disease are lacking. The data presented in this dissertation provide novel insight into the role of the sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate (S1P) pathways in the pathogenesis of PAH.

History

Advisor

Machado, Roberto F

Chair

Natarajan, Viswanathan

Department

Pharmacology

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

Dudek, Steven M Minshall, Richard D Tobacman, Larry S.

Submitted date

May 2018

Issue date

14/03/2018

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