title: Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function.
abstract: Cardiovascular diseases are associated with and/or caused by oxidative stress. This concept has been proven by using the approach of genetic deletion of reactive species producing (pro-oxidant) enzymes as well as by the overexpression of reactive species detoxifying (antioxidant) enzymes leading to a marked reduction of reactive oxygen and nitrogen species (RONS) and in parallel to an amelioration of the severity of diseases. Likewise, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of antioxidant RONS detoxifying enzymes. Thus, the consequences of the interaction (redox crosstalk) of superoxide/hydrogen peroxide produced by mitochondria with other ROS producing enzymes such as NADPH oxidases (Nox) are of outstanding importance and will be discussed including the consequences for endothelial nitric oxide synthase (eNOS) uncoupling as well as the redox regulation of the vascular function/tone in general (soluble guanylyl cyclase, endothelin-1, prostanoid synthesis). Pathways and potential mechanisms leading to this crosstalk will be analysed in detail and highlighted by selected examples from the current literature including hypoxia, angiotensin II-induced hypertension, nitrate tolerance, aging and others. The general concept of redox-based activation of RONS sources via "kindling radicals" and enzyme-specific "redox switches" will be discussed providing evidence that mitochondria represent key players and amplifiers of the burden of oxidative stress.
  
  
  
  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 for Cardiology, Laboratory of Molecular Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.affiliation: Center for Cardiology, Laboratory of Molecular Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelze
authors.affiliation: Center for Cardiology, Laboratory of Molecular Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Swenja
authors.initials: S
authors.lastname: Kröller-Schön
authors.affiliation: Center for Cardiology, Laboratory of Molecular 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 for Cardiology, Laboratory of Molecular Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schulz
authors.affiliation: Center for Cardiology, Laboratory of Molecular Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D016276:Ventricular Function
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases