{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:11:41Z","timestamp":1777939901431,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Jiangsu Natural Science Funds","award":["2016-870"],"award-info":[{"award-number":["2016-870"]}]},{"name":"Jiangsu Provincial Special Program of Medical Science","award":["BL2013001"],"award-info":[{"award-number":["BL2013001"]}]},{"name":"Nanjing science and Technology Committee","award":["201402045"],"award-info":[{"award-number":["201402045"]}]},{"name":"Jiangsu Six Talent Peaks","award":["2015-WSN-069"],"award-info":[{"award-number":["2015-WSN-069"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Norepinephrine (NE)\u2010mediated vasoconstriction plays an important role in pulmonary hypertension\u00a0associated with left heart disease (PH\u2010LHD). However, the role of NE\u2010mediated endothelial cell dysfunction in the pathogenesis of PH\u2010LHD remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      An enzyme\u2010linked immunosorbent assay showed that the NE concentration in the plasma of patients with PH\u2010LHD was higher and the nitrate\u2013nitrite concentration was lower than those in the control group. NE treatment decreased phospho\u2010Ser633\u2010eNOS and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenergic receptor (\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010AR) levels in the membrane of human pulmonary artery endothelial cells (HPAECs) analysed by western blot analysis. Consistently, fluorescence microscopy and flow cytometry showed that nitric oxide (NO) production was also decreased in HPAECs. Coimmunoprecipitation confirmed a direct interaction between \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010AR and endothelial NO synthase (eNOS). Overexpression of \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010AR attenuated the decline in phospho\u2010Ser633\u2010eNOS and NO production. Additionally, the expression of phospho\u2010Ser633\u2010eNOS and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010AR was decreased in human pulmonary artery endothelium. Finally, our results indicate that NE stimulated HPAEC proliferation, which was blocked by protein kinase A inhibitor or protein kinase B (PKB\u2013AKT) inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data provide a novel mechanism for NE\u2010decreased endothelium\u2010derived NO and NE\u2010induced HPAEC proliferation that leads to PH\u2010LHD, suggesting a potential therapeutic target for PH\u2010LHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.27057","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T12:14:04Z","timestamp":1534940044000},"page":"1842-1850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Norepinephrine stimulation downregulates the \u03b2\n                    <sub>2<\/sub>\n                    \u2010adrenergic receptor\u2013nitric oxide pathway in human pulmonary artery endothelial cells"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5379-2169","authenticated-orcid":false,"given":"Wande","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Cardiology Nanjing First Hospital, Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Nanjing First Hospital, Nanjing Medical University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PeiP","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Nanjing First Hospital, Nanjing Medical University Nanjing 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