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Lymphocyte‐specific adaptor protein, LNK, inhibits angiotensin II‐induced hypertension and inflammation
Author(s) -
Saleh Mohamed A.,
Harrison David G,
Madhur Meena S
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.708.15
Subject(s) - inflammation , medicine , endocrinology , cytokine , tumor necrosis factor alpha , angiotensin ii , peripheral blood mononuclear cell , blood pressure , immunology , biology , biochemistry , in vitro
Several large‐scale genome wide association studies have identified a number of loci associated with human hypertension. One such locus encodes the gene LNK, lymphocyte‐specific adaptor protein. The mechanism by which LNK contributes to blood pressure regulation is unknown. The objective of our study is to examine the role of LNK in angiotensin II (Ang)‐induced hypertension and inflammation. Using mice deficient in LNK (LNK −/− ), we found that loss of LNK results in an increase in tail cuff blood pressure after two weeks of Ang infusion (213±3.4 mmHg vs 177±6.1 mmHg, p<0.001). Renal inflammation was examined by staining for CD3, a marker of T cells. At baseline, LNK −/− exhibited slightly higher numbers of T cells in the cortex and medulla compared to wild type C57 mice (WT) and this was markedly increased in response to 2 weeks of Ang infusion. Cytokine analysis performed on the culture supernatants of splenic T cells demonstrated that baseline levels of interleukin (IL) 17A and F and tumor necrosis factor alpha were higher in LNK −/− mice compared to WT mice. The pro‐inflammatory cytokine, IL17A, was further increased in LNK −/− mice in response to Ang infusion while IL17F levels were decreased by Ang infusion. Taken together, these data demonstrate that LNK is a negative regulator of renal and systemic inflammation and inhibits Ang induced hypertension.