title: Targeting vascular (endothelial) dysfunction.
abstract: Cardiovascular diseases are major contributors to global deaths and disability-adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunction. Since vascular oxidative stress and inflammation are major determinants of endothelial function, we have also addressed current antioxidant and anti-inflammatory therapies. In the light of recent data that dispute the prognostic value of endothelial function in healthy human cohorts, we also discuss alternative diagnostic parameters such as vascular stiffness index and intima/media thickness ratio. We also suggest that assessing vascular function, including that of smooth muscle and even perivascular adipose tissue, may be an appropriate parameter for clinical investigations.
  
  
  
  This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.
authors.affiliation: Center of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
authors.affiliation: Center of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.|Center of Thrombosis and Hemostasis, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Steven
authors.affiliation: Center of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Weber
authors.affiliation: Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Shuvaev
authors.affiliation: Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ismail
authors.initials: I
authors.lastname: Laher
authors.affiliation: German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.|Department of Pharmacology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Huige
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cell Biology and Immunology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
authors.affiliation: Center of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants