{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:56:51Z","timestamp":1788947811261,"version":"build-2803163510"},"reference-count":119,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["1\/0035\/19 and 2\/0112\/19"],"award-info":[{"award-number":["1\/0035\/19 and 2\/0112\/19"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) is characterized by massive inflammation, increased vascular permeability and pulmonary edema. Mortality due to ARDS remains very high and even in the case of survival, acute lung injury can lead to pulmonary fibrosis. The renin\u2013angiotensin system (RAS) plays a significant role in these processes. The activities of RAS molecules are subject to dynamic changes in response to an injury. Initially, increased levels of angiotensin (Ang) II and des-Arg9-bradykinin (DABK), are necessary for an effective defense. Later, augmented angiotensin converting enzyme (ACE) 2 activity supposedly helps to attenuate inflammation. Appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair. ACE2 has been identified as a common target for different pathogens. Some Coronaviruses, including SARS-CoV-2, also use ACE2 to infiltrate the cells. A number of questions remain unresolved. The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-\u03b1 (TNF-\u03b1)-signaling is unclear. The roles of other non-classical RAS-associated molecules, e.g., alamandine, Ang A or Ang 1\u20139, also deserve attention. In addition, the impact of established RAS-inhibiting drugs on the pulmonary RAS is to be elucidated. The unfavorable prognosis of ARDS and the lack of effective treatment urge the search for novel therapeutic strategies. In the context of the ongoing SARS-CoV-2 pandemic and considering the involvement of humoral disbalance in the pathogenesis of ARDS, targeting the renin\u2013angiotensin system and reducing the pathogen\u2019s cell entry could be a promising therapeutic strategy in the struggle against COVID-19.<\/jats:p>","DOI":"10.3390\/ijms21218038","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T11:43:06Z","timestamp":1603885386000},"page":"8038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Renin\u2013Angiotensin System: An Important Player in the Pathogenesis of Acute Respiratory Distress Syndrome"],"prefix":"10.3390","volume":"21","author":[{"given":"Jaroslav","family":"Hrenak","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Inselspital \u2013 University Hospital of Bern, Freiburgstrasse 18, 3010 Bern, Switzerland"},{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9922-4885","authenticated-orcid":false,"given":"Fedor","family":"Simko","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia"},{"name":"3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, Limbova 5, 833 05 Bratislava, Slovakia"},{"name":"Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"key":"ref_1","unstructured":"ARDS Definition Task Force, Ranieri, V.M., Rubenfeld, G.D., Thompson, B.T., Ferguson, N.D., Caldwell, E., Fan, E., Camporota, L., and Slutsky, A.S. 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