{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T05:03:20Z","timestamp":1786770200230,"version":"build-2736575974"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["Collaborative Research Center 834"],"award-info":[{"award-number":["Collaborative Research Center 834"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,3]]},"abstract":"<jats:p>\n                    Atherosclerosis develops preferentially in areas of the arterial system, in which blood flow is disturbed. Exposure of endothelial cells to disturbed flow has been shown to induce inflammatory signaling, including NF-\u03baB activation, which leads to the expression of leukocyte adhesion molecules and chemokines. Here, we show that disturbed flow promotes the release of adrenomedullin from endothelial cells, which in turn activates its G\n                    <jats:sub>s<\/jats:sub>\n                    -coupled receptor calcitonin receptor\u2013like receptor (CALCRL). This induces antiinflammatory signaling through cAMP and PKA, and it results in reduced endothelial inflammation in vitro and in vivo. Suppression of endothelial expression of G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    , the \u03b1 subunit of the G-protein G\n                    <jats:sub>s<\/jats:sub>\n                    ; CALCRL; or adrenomedullin leads to increased disturbed flow\u2013induced inflammatory signaling in vitro and in vivo. Furthermore, mice with induced endothelial-specific deficiency of G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    , CALCRL, or adrenomedullin show increased atherosclerotic lesions. Our data identify an antiinflammatory signaling pathway in endothelial cells stimulated by disturbed flow and suggest activation of the endothelial adrenomedullin\/CALCRL\/G\n                    <jats:sub>s<\/jats:sub>\n                    system as a promising approach to inhibit progression of atherosclerosis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.140485","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T11:01:27Z","timestamp":1606906887000},"source":"Crossref","is-referenced-by-count":28,"title":["Disturbed flow\u2013induced Gs-mediated signaling protects against endothelial inflammation and atherosclerosis"],"prefix":"10.1172","volume":"5","author":[{"given":"Akiko","family":"Nakayama","sequence":"first","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-1435","authenticated-orcid":true,"given":"Juli\u00e1n","family":"Albarr\u00e1n-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth Anthony","family":"Roquid","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-4337","authenticated-orcid":true,"given":"Andr\u00e1s","family":"Iring","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Tonack","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8223-2638","authenticated-orcid":true,"given":"Oliver J.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Kiel, Kiel, and German Center for Cardiovascular Research (DZHK), Partner site Hamburg\/Kiel\/L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Heart and Lung Research, Department of Pharmacology, Bad Nauheim, Germany."},{"name":"Centre for Molecular Medicine, Medical Faculty, J.W. 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