{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T01:46:57Z","timestamp":1778982417050,"version":"3.51.4"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2008,9,8]],"date-time":"2008-09-08T00:00:00Z","timestamp":1220832000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Up-regulation of vascular endothelin type B (ET<jats:sub>B<\/jats:sub>) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, <jats:italic>ex vivo<\/jats:italic>, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ET<jats:sub>B<\/jats:sub> receptors in human internal mammary arteries.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using <jats:italic>in vitro<\/jats:italic> pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET<jats:sub>A<\/jats:sub> and ET<jats:sub>B<\/jats:sub> receptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The endohtelin-1-induced contraction (after endothelin ET<jats:sub>B<\/jats:sub> receptor desensitization) and the endothelin ET<jats:sub>A<\/jats:sub> receptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ET<jats:sub>B<\/jats:sub> receptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 \u03bcM bisindolylmaleimide I and 10 \u03bcM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1\/2) and C-jun terminal kinase (JNK) MAPK pathways (10 \u03bcM SB203580, 10 \u03bcM PD98059 and 10 \u03bcM SP600125, respectively).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ET<jats:sub>B<\/jats:sub> receptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ET<jats:sub>B<\/jats:sub> receptor changes in cardiovascular disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2261-8-21","type":"journal-article","created":{"date-parts":[[2008,9,9]],"date-time":"2008-09-09T06:13:34Z","timestamp":1220940814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways"],"prefix":"10.1186","volume":"8","author":[{"given":"David","family":"Nilsson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotta","family":"Gustafsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Wackenfors","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bodil","family":"Gesslein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Edvinsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Paulsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Ingemansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Malmsj\u00f6","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,9,8]]},"reference":[{"key":"201_CR1","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/348730a0","volume":"348","author":"H Arai","year":"1990","unstructured":"Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S: Cloning and expression of a cDNA encoding an endothelin receptor. 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