Mylinh La

Publications of Mylinh La

• Diagnosis and individual treatment of cardiovascular diseases: targeting vascular oxidative stress.

  Authors: Melanie E Armitage, Mylinh La, Harald Hhw Schmidt, Kirstin Wingler

  Expert review of clinical pharmacology. 09/2010; 3(5):639-48.

  Cardiovascular diseases are the leading cause of death and disability worldwide, yet we do not fully understand their underlying causes to reliably identify and treat, let alone prevent, theseCardiovascular diseases are the leading cause of death and disability worldwide, yet we do not fully understand their underlying causes to reliably identify and treat, let alone prevent, these diseases. The majority of therapeutic approaches are symptom orientated, and current practice often follows a 'one-fits-all' approach. New strategies are needed, which harness the potential of individualized medicine with its three major pillars: in vitro diagnostics for early identification of individuals at risk and monitoring of drug efficacy; molecular imaging for disease localization and monitoring; and innovative, mechanism-based drugs. One so far untargeted mechanism of cardiovascular disease is oxidative stress, that is, the increased occurrence of reactive oxygen species in the vascular wall that leads to endothelial dysfunction. We outline why previous antioxidant supplements do not work and suggest an alternative approach targeting the enzymatic sources of oxidative stress and using emerging biomarkers of oxidative stress. These and similar approaches may be applied to fewer patients but in a much more individualized, effective and cost-saving manner.

• Translating the oxidative stress hypothesis into the clinic: NOX versus NOS.

  Authors: Melanie Armitage, Kirstin Wingler, Harald Schmidt, Mylinh La

  Journal of molecular medicine (Berlin, Germany). 10/2009;

  Cardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeuticCardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeutic approaches are symptom-orientated. Knowing the molecular mechanism of disease would enable more targeted therapies. One postulated underlying mechanism of cardiovascular diseases is oxidative stress, i.e. the increased occurrence of reactive oxygen species such as superoxide. Oxidative stress leads to a dysfunction of vascular endothelium-dependent protective mechanisms. There is growing evidence that this scenario also involves impaired nitric oxide (NO)-cyclic GMP signalling. Out of a number of enzyme families that can produce reactive oxygen species, NADPH oxidases stand out, as they are the only enzymes whose sole purpose is to produce reactive oxygen species. This review focuses on the clinically validated targets of oxidative stress, NO synthase (NOS) and the NO receptor, soluble guanylate cyclase as well as the source of ROS, e.g. NADPH oxidases. We place recent knowledge in the function and regulation of these enzyme families into clinical perspective. For a comprehensive overview of the biology and pharmacology of oxidative stress and possible other sources and targets, we refer to other literature overviews.

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• Translating the oxidative stress hypothesis into the clinic: NOX versus NOS

  Authors: Melanie E Armitage, Kirstin Wingler, Harald H H W Schmidt, Mylinh La

  Cardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeuticCardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeutic approaches are symptom-orientated. Knowing the molecular mechanism of disease would enable more targeted therapies. One postulated underlying mechanism of cardiovascular diseases is oxidative stress, i.e. the increased occurrence of reactive oxygen species such as superoxide. Oxidative stress leads to a dysfunction of vascular endothelium-dependent protective mechanisms. There is growing evidence that this scenario also involves impaired nitric oxide (NO)-cyclic GMP signalling. Out of a number of enzyme families that can produce reactive oxygen species, NADPH oxidases stand out, as they are the only enzymes whose sole purpose is to produce reactive oxygen species. This review focuses on the clinically validated targets of oxidative stress, NO synthase (NOS) and the NO receptor, soluble guanylate cyclase as well as the source of ROS, e.g. NADPH oxidases. We place recent knowledge in the function and regulation of these enzyme families into clinical perspective. For a comprehensive overview of the biology and pharmacology of oxidative stress and possible other sources and targets, we refer to other literature overviews.