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Although several regulatory pathways have been identified, considerable knowledge gaps persist, and a unifying concept of the signaling pathways that underlie HPV and their impairment in lung diseases has not yet emerged. In the past, conceptual models of HPV have focused on pulmonary arterial smooth muscle cells (PASMC) acting as sensor and effector of hypoxia in the pulmonary vasculature. In contrast, the endothelium was considered a modulating bystander in this scenario. For an ideal design, however, the oxygen sensor in HPV should be located in the region of gas exchange, i.e., in the alveolar capillary network. This concept requires the retrograde propagation of the hypoxic signal along the endothelial layer of the vascular wall and subsequent contraction of PASMC in upstream arterioles that is elicited via temporospatially tightly controlled endothelial-smooth muscle cell crosstalk. The present review summarizes recent work that provides proof-of-principle for the existence and functional relevance of such signaling pathway in HPV that involves important roles for connexin 40, epoxyeicosatrienoic acids, sphingolipids, and cystic fibrosis transmembrane conductance regulator. Of translational relevance, implication of these molecules provides for novel mechanistic explanations for impaired ventilation\/perfusion matching in patients with pneumonia, sepsis, cystic fibrosis, and presumably various other lung diseases.<\/jats:p>","DOI":"10.1152\/japplphysiol.00120.2017","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T01:11:56Z","timestamp":1504228316000},"page":"1635-1646","source":"Crossref","is-referenced-by-count":68,"title":["The endothelium in hypoxic pulmonary vasoconstriction"],"prefix":"10.1152","volume":"123","author":[{"given":"Benjamin","family":"Grimmer","sequence":"first","affiliation":[{"name":"Institute of Physiology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang M.","family":"Kuebler","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin, 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