Are We Over Oxidized? Oxidative Stress, Cardiovascular Disease, and the Future of Intervention Studies with Antioxidants

A number of recent clinical trials with antioxidants, notably vitamin C and E, have provided no support for the commonly held view that increasing our intake of antioxidants will offset the ravages of cardiovascular disease as well as other diseases (for extensive critical reviews see: Kritharides and Stocker 2002; Antoniades et al 2003; Touyz 2004). Is this conclusion justified? The role of antioxidant dietary adjuncts and therapy in prevention and treatment remains a highly important clinical question. In this opinion article we address the question: Is there a future for antioxidant therapy in the treatment and prevention of cardiovascular disease? We conclude that there is a need for better-designed studies as well as a re-thinking of the choice of antioxidants

Role of NADPH Oxidase-4 in human endothelial progenitor cells

Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood. Methods: EPCs were isolated from human saphenous vein and mammary artery discarded during bypass surgery. NOX4 gene and protein expression in EPCs were measured by real time-PCR and Western blot analysis respectively. NOX4 gene expression was inhibited using an adenoviral vector expressing human NOX4 shRNA (Ad-NOX4i). H2O2 production was measured by Amplex red assay. EPC migration was evaluated using a transwell migration assay. EPC proliferation and viability were measured using trypan blue counts. Results: Inhibition of NOX4 using Ad-NOX4i reduced Nox4 gene and protein expression as well as H2O2 formation in EPCs. Inhibition of NOX4-derived H2O2 decreased both proliferation and migration of EPCs. Interestingly, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) decreased NOX4 expression and reduced survival of EPCs. However, the survival of EPCs was further diminished by TNF-α in NOX4-knockdown cells, suggesting that NOX4 has a protective role in EPCs. Conclusion: These findings suggest that NOX4-type NADPH oxidase is important for proliferation and migration functions of EPCs and protects against pro-inflammatory cytokine induced EPC death. These properties of NOX4 may facilitate the efficient function of EPCs which is vital for successful neovascularization

Opinion - Are we over oxidized? Oxidative stress, cardiovascular disease, and the future of intervention studies with antioxidants

Greg J Dusting1, Chris Triggle21Howard Florey Institute, University of Melbourne, VIC, Australia; 2School of Medical Sciences, RMIT University, VIC, AustraliaAre we over oxidized? A number of recent clinical trials with antioxidants, notably vitamin C and E, have provided no support for the commonly held view that increasing our intake of antioxidants will offset the ravages of cardiovascular disease as well as other diseases (for extensive critical reviews see: Kritharides and Stocker 2002; Antoniades et al 2003; Touyz 2004). Is this conclusion justified? The role of antioxidant dietary adjuncts and therapy in prevention and treatment remains a highly important clinical question. In this opinion article we address the question: Is there a future for antioxidant therapy in the treatment and prevention of cardiovascular disease? We conclude that there is a need for better-designed studies as well as a re-thinking of the choice of antioxidants