title: Linking inflammation and hypertension via LNK/SH2B3.
abstract: OBJECTIVE
  Hypertension is a leading cause of cardiovascular and renal morbidity, and mortality. Genome-wide association studies identified a single-nucleotide polymorphism in the gene SH2B3 encoding the lymphocyte adaptor protein, LNK, but, until recently, little was known about how LNK contributes to hypertension. This review summarizes recent work highlighting a central role for LNK in inflammation and hypertension.
  
  
  RESULTS
  Using a systems biology approach that integrates genomic data with whole blood transcriptomic data and network modeling, LNK/SH2B3 was identified as a key driver gene for hypertension in humans. LNK is an intracellular adaptor protein expressed predominantly in hematopoietic and endothelial cells that negatively regulates cell proliferation and cytokine signaling. Genetic animal models with deletion or mutation of LNK revealed an important role for LNK in renal and vascular inflammation, glomerular injury, oxidative stress, interferon-γ production, and hypertension. Bone marrow transplantation experiments revealed that LNK in hematopoietic cells is primarily responsible for blood pressure regulation.
  
  
  CONCLUSIONS
  LNK/SH2B3 is a key driver gene for human hypertension, and alteration of LNK in animal models has a profound effect on inflammation and hypertension. Thus, LNK is a potential therapeutic target for this disease and its devastating consequences.
authors.affiliation: aDepartment of Molecular Physiology and Biophysics bDepartment of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Dale
authors.forename: Meena S
authors.initials: MS
authors.lastname: Madhur
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001794:Blood Pressure; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000503:physiopathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C490778:SH2B3 protein, human; C097176:Sh2b3 protein, rat; D007371:Interferon-gamma