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Permeability

Hypertension Glucose Cholesterol risk factors. Healthy endothelium. Cytokines Chemokines TNF-a, MCP-1. Non-adhesive. ICAMs. NO NOS NO. Permeability. Permeability. selectins. Oxidases. NOS inhibitors. ROS. Cytokines Growth factors.

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Permeability

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  1. Hypertension Glucose Cholesterol risk factors Healthy endothelium Cytokines Chemokines TNF-a, MCP-1 Non-adhesive ICAMs NO NOS NO Permeability Permeability selectins Oxidases NOS inhibitors ROS Cytokines Growth factors

  2. phenotyping - inflammation and oxidative stress hypertension Oxidativestress Micro-inflammation

  3. Monocyt Neutrophile + Thrombocyt-adhesion LDL Thrombus formation Cytokines Growth Factors Endothelium Foam cell Smooth muscle cell Proliferation Inflammation and the pathogenesis of vascular disease

  4. Inflammatory Biomarkers

  5. hsCRP and cardiovascular risk Ridker PM et al. Circulation 2003; 107: 363

  6. Inflammatory Biomarkers

  7. phenotyping - inflammation and oxidative stress hypertension Oxidativestress Micro-inflammation

  8. Reactive oxygen species damage the endothelium Nitric oxide synthase iNOS Endothelial injury

  9. Reactive Oxygen Species (ROS) • Superoxide (O2.-) • Hydrogen Peroxide (H2O2) • Hydroxyl Radical (OH.) - product of Fenton reaction catalyzed by free Fe and Cu • Singlet Oxygen (1DgO2) - oxygen at an excited state, requiring photosensitizers and photons

  10. Biomarkers for oxidative stress

  11. Fatal and non fatal cardiovascular events All cause mortality 1.0 1.0 .9 .9 .8 .8 Cumulative survival .7 .7 .6 .6 .5 .5 0 6.7 13.3 20.0 26.7 33.3 40.0 46.7 0 6.7 13.3 20.0 26.7 33.3 40.0 46.7 Time (months) Time (months) ADMA and cardiovascular mortality <50th percentile <50th percentile 50th –75th percentile 50th –75th percentile >75th percentile >75th percentile * Fully adjusted for traditional and non traditional risk factors * Fully adjusted for traditional and non traditional risk factors Zoccali et al. Lancet 358:2113-7, 2001

  12. Reactive Oxygen Species (ROS) Koyametal et al. Mol Med 13: 625 - 635, 2007

  13. no phenotyping without patients and families ! hypertension Oxidativestress Micro-inflammation

  14. Blood pressure,hsCRP and microalbuminuria PREVEND Study (n = 8,592) Stuveling EM et al. Hypertension 2004; 43: 791

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