Oxidant Generation Predominates Around Calcifying Foci and Enhances Progression of Aortic Valve Calcification

• DOI: 10.1161/atvbaha.107.156745
• Publication Date: 2007-12-28T01:44:11Z
• Authors: Marcel Liberman; Estêvão Bassi; Marina Kamla Mart...; Fábio Cerqueira ...; João Wosniak; Pablo M.A. Pomera...; Francisco R.M. La...
• Keywords: NAD(P)H oxidase; NOX4; NOX1; P22phox

We hypothesized that reactive oxygen species (ROS) contribute to progression of aortic valve (AV) calcification/stenosis.We investigated ROS production and effects antioxidants tempol lipoic acid (LA) in calcification rabbits given 0.5% cholesterol diet +10(4) IU/d Vit.D2 for 12 weeks. Superoxide H2O2 microfluorotopography 3-nitrotyrosine immunoreactivity showed increased signals not only macrophages but preferentially around calcifying foci, cells expressing osteoblast/osteoclast, macrophage markers. Such also expression NAD(P)H oxidase subunits Nox2, p22phox, protein disulfide isomerase. Nox4, Nox1 mRNA, was increased. Tempol augmented whereas LA decreased signals. Importantly, AV calcification, assessed by echocardiography histomorphometry, 43% 70% with LA, (P < or = 0.05). further enhanced apoptosis Nox4 expression. In human sclerotic stenotic AV, we found analogous increases foci. An vitro vascular smooth muscle cell (VSMC) model exhibited increased, catalase-inhibitable, calcium deposit tempol, LA.Our data provide evidence ROS, particularly hydrogen peroxide, potentiate progression. However, a paradoxical effect, exacerbating AV/vascular likely because its induced increase peroxide generation.