Lipoic acid decreased aortic valve calcification by 43% to 70%, whereas tempol paradoxically exacerbated calcification by increasing peroxide generation (P<=0.05).
Does treatment with antioxidants tempol or lipoic acid reduce the progression of aortic valve calcification in a rabbit model?
Reactive oxygen species potentiate aortic valve calcification, which can be attenuated by lipoic acid but paradoxically exacerbated by tempol.
p-value: p=< or = 0.05
OBJECTIVE: We hypothesized that reactive oxygen species (ROS) contribute to progression of aortic valve (AV) calcification/stenosis. METHODS AND RESULTS: We investigated ROS production and effects of antioxidants tempol and lipoic acid (LA) in calcification progression in rabbits given 0.5% cholesterol diet +10(4) IU/d Vit.D2 for 12 weeks. Superoxide and H2O2 microfluorotopography and 3-nitrotyrosine immunoreactivity showed increased signals not only in macrophages but preferentially around calcifying foci, in cells expressing osteoblast/osteoclast, but not macrophage markers. Such cells also showed increased expression of NAD(P)H oxidase subunits Nox2, p22phox, and protein disulfide isomerase. Nox4, but not Nox1 mRNA, was increased. Tempol augmented whereas LA decreased H2O2 signals. Importantly, AV calcification, assessed by echocardiography and histomorphometry, decreased 43% to 70% with LA, but increased with tempol (P < or = 0.05). Tempol further enhanced apoptosis and Nox4 expression. In human sclerotic or stenotic AV, we found analogous increases in ROS production and NAD(P)H oxidase expression around calcifying foci. An in vitro vascular smooth muscle cell (VSMC) calcification model also exhibited increased, catalase-inhibitable, calcium deposit with tempol, but not with LA. CONCLUSIONS: Our data provide evidence that ROS, particularly hydrogen peroxide, potentiate AV calcification progression. However, tempol exhibited a paradoxical effect, exacerbating AV/vascular calcification, likely because of its induced increase in peroxide generation.
Liberman et al. (Fri,) conducted a other in Aortic valve calcification/stenosis. Antioxidants tempol and lipoic acid (LA) was evaluated on Aortic valve calcification assessed by echocardiography and histomorphometry (p=< or = 0.05). Lipoic acid decreased aortic valve calcification by 43% to 70%, whereas tempol paradoxically exacerbated calcification by increasing peroxide generation (P<=0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: