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dc.rights.licenseCC-BY-NC-ND
dc.contributor.advisorvan Emst, M.
dc.contributor.authorElema, A.
dc.date.accessioned2014-07-21T17:00:38Z
dc.date.available2014-07-21T17:00:38Z
dc.date.issued2014
dc.identifier.urihttps://studenttheses.uu.nl/handle/20.500.12932/16970
dc.description.abstractDegenerative (myxomatous) mitral valve disease is a leading cause of disability and death in dogs and humans. Transforming growth factor-beta 1 (TGFβ1) is strongly implicated in the pathogenesis of degenerative mitral valve disease, however initiating stimuli and signaling mechanisms that mediate TGFβ1 expression in mitral valves are not known. This study tested the hypothesis that high tensile strain on mitral valves initiates local synthesis of serotonin and angiotensin II, and that these in turn would act synergistically to increase TGFβ1 expression. Methods and Results: Cultured sheep mitral valves were subjected to 0% (control), 10% (low physiologic), 20% (high physiologic), and 30% (pathologic) cyclic strain for 24 and 72 h in serum-free culture media. Serotonin and angiotensin II concentrations were measured in the culture media by ELISA. TGFβ1 abundance was measured by Western blot. Angiotensin II levels were significantly decreased in the media at every step of increasing strain at 24 h and between 10 % and 20% strained mitral valves at 72 h. Serotonin levels were significantly increased in the media of 20% and 30% strained mitral valves at 24 and 72 h. Pharmacologic inhibition of serotonin with 10 μM SB-206553 (serotonin type 2 receptor blocker) diminished expression of TGFβ1 in 30% strained mitral valves. Conclusion: Serotonin mediates cyclic strain-induced expression of TGFβ1 in mitral valves. The role of angiotensin is uncertain. These results could point to possible therapeutic strategies to slow progression of degenerative mitral valve disease.
dc.description.sponsorshipUtrecht University
dc.format.extent289753
dc.format.mimetypeapplication/zip
dc.language.isoen
dc.titleSerotonin, and probably not Angiotensin II, mediates cyclic strain-induced expression of transforming growth factor-beta 1 in mitral valves.
dc.type.contentDoctoral Thesis
dc.rights.accessrightsOpen Access
dc.subject.keywordsDegenerative myxomatous mitral valve disease; Transforming growth factor-beta 1 (TGFβ1); Angiotensin II; Serotonin; Strain;
dc.subject.courseuuGeneeskunde van gezelschapsdieren


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