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The Role of CD70 in Vascular Function
Author(s) -
Itani Hana A.,
Pandey Arvind,
Brown Jonathan D.,
Harrison David G.
Publication year - 2017
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.31.1_supplement.854.9
Subject(s) - enos , nitric oxide , vasodilation , sodium nitroprusside , nitric oxide synthase , endothelium , vascular smooth muscle , acetylcholine , medicine , t cell , biology , endocrinology , microbiology and biotechnology , immune system , chemistry , immunology , smooth muscle
We have recently shown that CD70 is important in formation of effector memory T (T EM ) cells in hypertension and T EM cells enhance the hypertensive response and end organ damage caused by repeated hypertensive stimuli. CD70 has traditionally been identified on antigen presenting cells and interacts with CD27 on T cells, promoting proliferation and memory cell formation. The precise cell types that express CD70 and the role of CD70 on non‐immune cells has not previously been investigated. Here we discovered a new role of CD70 in vascular function. Studies of mesenteric vascular reactivity showed that CD70 −/− mice have markedly impaired endothelium‐dependent vasodilatation to acetylcholine compared to WT mice (44± 3 vs 25 ± 4%) at baseline. In contrast, there were no differences in relaxation responses to sodium nitroprusside. Pre‐incubating vessels with the endothelial nitric oxide synthase (eNOS) inhibitor L‐NAME blocked endothelium‐dependent vasodilatation to acetylcholine in WT mice by 50%, in contrast, L‐NAME had no effect on endothelial vessel relaxation in CD70 −/− mice. This suggests that vessels of CD70 −/− mice lack the capacity to produce nitric oxide. Western blots for the endothelial nitric oxide synthase (eNOS) showed a marked reduction of this enzyme in the aortas of CD70 −/− as compared to wild type mice. In additional experiments, we showed that human umbillical vein endothelial cells express CD70 mRNA and that this is increased by > 30 fold by laminar (15 dynes/cm 2 ) compared to oscillatory shear. Finally, using immunohistochemistry, we identified CD70 protein localized to resistance vessels of the kidney of ang II‐treated mice. These data define a new role of CD70 in modulating vascular function. Expression of CD70 might contribute to the previously identified ability of endothelial cells to present antigen to T cells and promote T cell activation and T EM cell formation. Moreover, CD70 seems to be linked to eNOS expression by mechanisms that remain to be defined.