Deciphering the molecular mechanisms of pulmonary hypoxia and its health sequelae: proceedings of the first international DECIPHER symposium on pulmonary hypoxia,Iquique,Chile,16–17 October 2019

Hypoxia is a major threat for the integrity of every cell as well as for the organism as a whole. It is therefore not surprising that regulatory mechanisms have evolved to compensate reduced oxygen supply for more or less limited periods of time. One such mechanism by which the human body compensates phases of reduced ventilation of parts of the lung is hypoxic pulmonary vasoconstriction (HPV). First described in the 1940s by the Swedish Physiologist, Ulf van Euler, and his co-worker from Pharmacology, Göran Liljestrand, ¹ this effect, which can be found as the Euler-Liljestrand mechanism in any Physiology textbook, has been a topic of research into the exact molecular mechanisms behind it. HPV contributes to many pulmonary diseases, especially in advanced stages, and may be a cause of pulmonary hypertension, right ventricular hypertrophy, and heart failure. Chronic hypoxia as it may occur at high altitude serves as a model for such lung diseases, which allows to better dissect the pathophysiological consequences of HPV from other pathophysiological events occurring in lung diseases, such as inflammation and fibrosis.

Chronic intermittent hypoxia (CIH) is a common model of professional exposure to altitude for workers in the mining areas of the Andean high plateau, where the incidence of pulmonary arterial hypertension is higher by several orders of magnitude compared to Western Europe. At the same time, CIH may serve as a model disease to study the health consequences and its molecular mechanisms of hypoxia in a translational approach in humans.

These were the reasons for us to submit a research proposal together with our colleagues from Iquique, Chile, and the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany) to the German federal government’s Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), in 2017. After two years of successful bi-national work in the project DECIPHER (Deutsch-chilenisches Institut zur Erforschung der pulmonalen Hypoxie und ihrer Folgeerkrankungen; German-Chilean Institute for Research on Pulmonary Hypoxia and its Health Sequelae), we organized an international scientific symposium in Iquique, Chile, on 16 and 17 October 2019. The present issue of Pulmonary Circulation gives an overview of the topics that were covered during this symposium: The epidemiology of CIH-related disease was addressed, marking the importance of this type of hypoxic exposure for the Andean population. Clinical risk markers for hypoxia-induced disease were discussed that help to understand common pathophysiological links with other cardiometabolic diseases. The role of alveolar epithelial sodium channels, pulmonary endothelial cell L-arginine and dimethylarginine metabolic pathways, and vascular smooth muscle cell calcium regulation were matters of intense discussion, as was the possible nature of the oxygen sensor. Hypoxia as a cause of persistent pulmonary hypertension of the newborn is a matter of epidemiological and clinical concern in the Andean region, as is the contribution and treatment of pulmonary hypoxia in lung diseases in Western Europe. Thus, the symposium span a wide range of topics, all relating to pulmonary hypoxia, and thereby opened the doors for DECIPHER to develop into a multilateral, multi-national research network during the next three years of public funding.

As principal investigators of the DECIPHER project, we are proud to announce that in 2019, our project developed into a virtual bilateral research institute with our Chilean partners. The DECIPHER network is open to welcome other research groups, both academic and commercial, that are interested in the topic of pulmonary hypoxia and its health sequelae, that are willing to share efforts for deciphering the molecular mechanisms of pulmonary hypoxia, and that are able to bring to the network more scientific diversity and expertise. We are grateful to the BMBF for generous support for building the infrastructures allowing us to develop lasting structures of research collaboration, and for allowing us to more prominently present German research activities in the international community, not least, through this special issue of Pulmonary Circulation, which was made possible by DECIPHER funds. We are also grateful to our first DECIPHER Network partner, CODELCO, for co-funding the symposium.