title: Suppression of JAK2/STAT3 signaling reduces end-to-end arterial anastomosis induced cell proliferation in common carotid arteries of rats.
abstract: BACKGROUND
  JAK2/STAT3 pathway was reported to play an essential role in the neointima formation after vascular intima injury. However, little is known regarding this pathway to the whole layer injury after end-to-end arterial anastomosis (AA). Here, we investigated the role of JAK2/STAT3 pathway in common carotid arterial (CCA) anastomosis-induced cell proliferation, phenotypic change of vascular smooth muscle cells (VSMCs) and re-endothelialization.
  
  
  METHODS
  CCAs of adult male Wistar rats were resected at 3, 7, 14, and 30 days after end-to-end CCA anastomosis. Activation of JAK2/STAT3 pathway was detected by Western blotting and Immunofluorescence, and expression of proliferating cell nuclear antigen (PCNA) was detected by Q-PCR and Western blotting. Under the treatment with AG490 (a JAK2 inhibitor), protein levels of JAK2, STAT3 and PCNA, morphological changes of artery, phenotypic change of VSMCs, and re-endothelialization were measured by Western blotting, H&E, Q-PCR, and Evans blue staining respectively.
  
  
  RESULTS
  The protein levels of p-JAK2, p-STAT3, and PCNA were up-regulated, peaked on the 7(th) day in the vessel wall after AA. AG490 down-regulated the levels of p-JAK2, p-STAT3, and PCNA on the 7(th)-day-group, resulting in reduced vessel wall proliferation on the 7(th) and 14(th) day after AA. Besides, AG490 switched the phenotypic change of VSMCs after AA representing inhibited mRNA levels of synthetic phase markers (osteopoitin and SMemb) and up-regulated contractile phase markers (ASMA, SM2 and SM22α). Furthermore, AG490 did not affect the re-endothelialization process on all indicated time points after AA (the 3(rd), 7(th), 14(th), and 30(th) day).
  
  
  CONCLUSIONS
  Our study indicated that JAK2/STAT3 signaling pathway played an important role on cell proliferation of the injured vessel wall, and probably a promising target for the exploration of drugs increasing the patency or reducing the vascular narrowness after AA.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Jinbing
authors.initials: J
authors.lastname: Zhao
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xingfen
authors.initials: X
authors.lastname: Su
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Chunhua
authors.initials: C
authors.lastname: Hang
mesh_terms: D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D002339:Carotid Arteries / Q000166:cytology* / Q000378:metabolism / Q000601:surgery*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D053614:Janus Kinase 2