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The Protective Role of Suppressor of Cytokine Signaling 3 (SOCS3) Against Angiotensin II‐Induced Endothelial Dysfunction
Author(s) -
Li Ying,
Johnson Andrew,
Kinzenbaw Dale,
Faraci Frank
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.708.14
Subject(s) - socs3 , angiotensin ii , endothelial dysfunction , endocrinology , endothelium , medicine , vasodilation , stat3 , cytokine , acetylcholine , nitric oxide , superoxide , vasoprotective , chemistry , pharmacology , signal transduction , receptor , biochemistry , enzyme
Angiotensin II (Ang II) plays a major role in vascular disease and hypertension, in part, through the interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) pathway. Although SOCS3 is a known regulator of this pathway in the immune system, its role in vascular disease and hypertension is unknown. We hypothesized that SOCS3 protects against Ang II‐induced endothelial dysfunction. Responses of carotid arteries from SOCS3 haplodeficient mice (SOCS3 +/− ) and wild‐type (WT) littermates were examined after 22 hrs incubation with vehicle or Ang II (1 nmol/L). Relaxation to acetylcholine (Ach, endothelium‐dependent) was similar in all arteries incubated with vehicle. This low concentration of Ang II did not affect Ach‐induced vasodilation in WT, but reduced that of SOCS3 +/− mice by ~50% (P<0.05). This Ang II‐induced impairment was prevented by co‐incubation with S3I‐201 (a small molecular inhibitor of STAT3) or an anti‐IL‐6 antibody or tempol, a scavenger of superoxide. Responses to nitroprusside were similar in all groups. These data suggest that reductions in SOCS3 expression do not alter vascular function under baseline conditions but predispose to Ang II‐induced endothelial dysfunction. Thus, SOCS3 may normally protect endothelium by inhibiting IL‐6/STAT3 signaling. This work was supported by NIH grants NS24621 and HL62984.