Regulation of vascular function and inflammation via crosstalk of reactive oxygen and nitrogen species from mitochondria or NADPH oxidase

Abstract

Oxidative stress plays a key role for the development of cardiovascular, metabolic and neurodegenerative disease. 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. Vice versa, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of antioxidant RONS detoxifying enzymes. We have previously identified crosstalk mechanisms between different sources of RONS, which can amplify the oxidative stress signal. Pathways and potential mechanisms leading to this crosstalk will be analysed in detail and highlighted by selected examples from the current literature and own data 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” as well as the interaction with redox‐sensitive inflammatory pathways will be discussed. An outlook will be provided with preliminary data on the existence of such crosstalk in the setting of diabetes but also mouse models of cardiovascular dysfunction triggered by environmental noise exposure.Support or Funding InformationThe present work was supported by the European Cooperation in Science and Technology (COST Action BM1203/EU‐ROS), by generous financial support by the “Stiftung Mainzer Herz”, by the Centre of Translational Vascular Biology (CTVB), by “NMFZ” and “Stufe 1” funds from the Johannes Gutenberg University Mainz.Crosstalk between different sources of ROS and RNS (mitochondria, NADPH oxidases, xanthine oxidase and NO synthase). Superoxide/hydrogen peroxide formation by any source may be triggered by oxidative stress from all other ROS sources via redox‐activation of multiple mechanisms. From Daiber et al. BJP 2017.Figure 1