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Characterization and mechanisms of redox imbalance in pathophysiology of degenerative aortic valve stenosis

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Author(s):
Marcel Liberman
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Francisco Rafael Martins Laurindo; Dulcineia Saes Parra Abdalla; Kleber Gomes Franchini; Paulo Ferreira Leite; Flavio Tarasoutchi
Advisor: Francisco Rafael Martins Laurindo
Abstract

To invetigate whether oxidative stress contributes to aortic valve (AV) calcification/stenosis progression, we assessed reactive oxygen species (ROS) production and effects of antioxidants tempol and lipoic acid in a rabbit AV calcification model. Superoxide, H2O2 and 3-nitrotyrosine increased in inflammatory cells and mainly in calcifying nuclei, coincident with NADPH oxidase subunits p22phox, Nox2 and protein disulfide isomerase, which co-localized. PCR showed switch from Nox1 to Nox4. Calcification was smaller with lipoic acid and greater with tempol, similar to an in vitro smooth muscle cell calcification model results. Human stenotic AV had analogous increase in ROS and protein expression around calcifying nuclei. Oxidative stress can contribute to AV stenosis progression. (AU)