Endothelin-1 in humans is increased by oxygen-derived radicals ex vivo and in vivo
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Endothelin-1 in humans is increased by oxygen-derived radicals ex vivo and in vivo. / Knappe, Dorit; Sill, Bjoern; Tharun, Bjoern; Koester, Ralf; Baldus, Stephan; Muenzel, Thomas; Meinertz, Thomas; Kähler, Jan.
in: J INVEST MED, Jahrgang 55, Nr. 6, 09.2007, S. 306-314.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Endothelin-1 in humans is increased by oxygen-derived radicals ex vivo and in vivo
AU - Knappe, Dorit
AU - Sill, Bjoern
AU - Tharun, Bjoern
AU - Koester, Ralf
AU - Baldus, Stephan
AU - Muenzel, Thomas
AU - Meinertz, Thomas
AU - Kähler, Jan
PY - 2007/9
Y1 - 2007/9
N2 - Endothelin-1, angiotensin II, and oxygen-derived radicals are pivotal factors in the development and progression of atherosclerosis. In vitro studies suggest that generation of oxygen-derived radicals by angiotensin II is an important mechanism increasing endothelin-1 synthesis, which consecutively may trigger effects such as cell proliferation and hypertrophy. The aim of this study was to confirm our previous data in an ex vivo and an in vivo setting. Explanted segments of internal mammary arteries were analyzed for big endothelin-1 expression following incubation with xanthine oxidase, angiotensin II, superoxide dismutase, and catalase to stimulate or to specifically inactivate oxygen-derived radicals. Endothelin-1 concentrations were determined by immunostaining and enzyme-linked immunosorbent assay. Further, oxypurinol was given to patients undergoing coronary angioplasty, a procedure known to increase plasma endothelin-1 concentrations. Angiotensin II and xanthine oxidase dose-dependently increased big endothelin-1 concentrations (p < .01 and p < .0001); the effects could be inhibited by coincubation with superoxide dismutase and catalase as determined by both semiquantitative immunofluorescence and enzyme-linked immunosorbent assay (p < .01). Patients undergoing coronary angioplasty exhibited significantly elevated big endothelin-1 concentrations 60 minutes after angioplasty (p = .03); in patients also receiving oxypurinol immediately after angioplasty, big endothelin-1 concentrations decreased (p = .001). Our results may explain the association between elevated angiotensin II levels, increased oxidative stress, and increased endothelin-1 concentrations in atherosclerosis. The data therefore support the concept that oxygen-derived free radicals stimulate the release of endothelin-1, which subsequently induces effects such as proliferation and enhanced agonist-induced vasoconstriction, previously attributed directly to angiotensin II.
AB - Endothelin-1, angiotensin II, and oxygen-derived radicals are pivotal factors in the development and progression of atherosclerosis. In vitro studies suggest that generation of oxygen-derived radicals by angiotensin II is an important mechanism increasing endothelin-1 synthesis, which consecutively may trigger effects such as cell proliferation and hypertrophy. The aim of this study was to confirm our previous data in an ex vivo and an in vivo setting. Explanted segments of internal mammary arteries were analyzed for big endothelin-1 expression following incubation with xanthine oxidase, angiotensin II, superoxide dismutase, and catalase to stimulate or to specifically inactivate oxygen-derived radicals. Endothelin-1 concentrations were determined by immunostaining and enzyme-linked immunosorbent assay. Further, oxypurinol was given to patients undergoing coronary angioplasty, a procedure known to increase plasma endothelin-1 concentrations. Angiotensin II and xanthine oxidase dose-dependently increased big endothelin-1 concentrations (p < .01 and p < .0001); the effects could be inhibited by coincubation with superoxide dismutase and catalase as determined by both semiquantitative immunofluorescence and enzyme-linked immunosorbent assay (p < .01). Patients undergoing coronary angioplasty exhibited significantly elevated big endothelin-1 concentrations 60 minutes after angioplasty (p = .03); in patients also receiving oxypurinol immediately after angioplasty, big endothelin-1 concentrations decreased (p = .001). Our results may explain the association between elevated angiotensin II levels, increased oxidative stress, and increased endothelin-1 concentrations in atherosclerosis. The data therefore support the concept that oxygen-derived free radicals stimulate the release of endothelin-1, which subsequently induces effects such as proliferation and enhanced agonist-induced vasoconstriction, previously attributed directly to angiotensin II.
KW - Angiotensin II/pharmacology
KW - Catalase/metabolism
KW - Endothelin-1/blood
KW - Fluorescent Antibody Technique
KW - Free Radical Scavengers/pharmacology
KW - Free Radicals/metabolism
KW - Humans
KW - In Vitro Techniques
KW - Mammary Arteries/drug effects
KW - Oxidative Stress
KW - Oxypurinol/pharmacology
KW - Reactive Oxygen Species/metabolism
KW - Superoxide Dismutase/metabolism
KW - Xanthine/metabolism
KW - Xanthine Oxidase/metabolism
U2 - 10.2310/6650.2007.00013
DO - 10.2310/6650.2007.00013
M3 - SCORING: Journal article
C2 - 17963680
VL - 55
SP - 306
EP - 314
JO - J INVEST MED
JF - J INVEST MED
SN - 1081-5589
IS - 6
ER -
