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CD40 ligand contributes to angiotensin‐II induced vascular inflammation, oxidative stress and endothelial dysfunction
Author(s) -
Daub Steffen,
Hausding Michael,
Jurk Kerstin,
Becker Christian,
KroellerSchoen Swenja,
Oelze Matthias,
Schwenk Melanie,
Stein Judith,
Kerahrodi Jasmin Ghaemi,
Kossmann Sabine,
Schulz Eberhard,
Wenzel Philip,
ReskeKunz Angelika,
Münzel Thomas,
Grabbe Stephan,
Daiber Andreas
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.708.13
Subject(s) - angiotensin ii , oxidative stress , medicine , cd40 , endocrinology , endothelial dysfunction , inflammation , nadph oxidase , reactive oxygen species , nox4 , p22phox , chemistry , biology , receptor , biochemistry , in vitro , cytotoxic t cell
Methods and Results Angiotensin‐II (1mg/kg/d for 7d) was infused in C57/Bl6 (control) and CD40L −/− mice using osmotic minipumps. Vascular function was recorded by isometric tension studies, reactive oxygen species (ROS) were monitored in blood and heart of the mice by enhanced chemiluminescence. ELISA of CD4 + T cell supernatants, Western blot analysis and real‐time RT‐PCR were used to analyze pro‐inflammatory cytokines, NAPDH oxidase subunits, T cell transcription factors and other genes of interest. CD40L −/− mice showed an ameliorated endothelial function and decreased oxidative stress in the heart and blood after angiotensin‐II treatment compared to their wild‐type littermates. Moreover, CD40L −/− mice displayed significantly decreased levels of T H 1 cytokines released by splenic CD4 + T cells. This observation was accompanied by lower expression levels of NOX‐2 in aortic tissue, T‐bet in splenic cells, as well as P‐selectin in heart tissue from CD40L −/− mice. Conclusions Our results demonstrate that CD40L −/− deficiency improves angiotensin‐II induced vascular inflammation, dysfunction and oxidative stress. These data further support our previous observations [Wenzel et al. Circulation, 2011] that immune cells and inflammatory pathways significantly contribute to angiotensin‐II induced arterial hypertension. Research support This work was supported by funds from the Federal Ministry of Education and Research (BMBF 01EO1003) to A.D., S.G., P.W. and T.M; S.K.‐S., E.S., A.D. and T.M. hold grants from the Stiftung Mainzer Herz.