1. Academic Validation
  2. EphB4 signaling maintains the contractile phenotype of adult venous smooth muscle cells

EphB4 signaling maintains the contractile phenotype of adult venous smooth muscle cells

  • Am J Transl Res. 2020 Aug 15;12(8):4522-4531.
Chenzi Yang 1 2 Chang Shu 1 2 3 Lunchang Wang 1 2 Xin Li 1 2 Hao He 1 2 Jiehua Li 1 2 Jieting Zhu 1 2 Yibo Yang 4 Alan Dardik 5
Affiliations

Affiliations

  • 1 Department of Vascular Surgery, The Second Xiangya Hospital of Central South University Changsha, Hunan, China.
  • 2 Vascular Disease Institute, Central South University Changsha, Hunan, China.
  • 3 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Science, Peking Union Medical College Beijing, China.
  • 4 Department of Sport Surgery and Sport Medicine, Hunan Provincial People's Hospital Changsha, Hunan, China.
  • 5 Department of Surgery, Yale School of Medicine New Haven, CT, USA.
PMID: 32913525
Abstract

Background: Autologous vein grafting remains the gold standard for surgical bypass grafts. However, vein bypasses still have significant incidence of failure. Ephrin type-B receptor 4 (EphB4), the embryonic venous determinant, may modulate vein graft adaptation. Although EphB4 is expressed in venous endothelial and smooth muscle cells (SMCs), it is not known whether EphB4 is functional in human SMCs.

Materials and methods: Human adult venous SMCs were obtained from the inferior vena cava of an adult human liver donor. Primary SMCs were stimulated with EphrinB2/Fc or transfected with an EphB4-expression vector (GV219-EphB4). Expression of SMC phenotype markers, migration, and proliferation were evaluated.

Results: Activation of EphB4 with EphrinB2/Fc increased the mRNA and protein expression of the venous SMC contractile markers alpha actin, calponin-1, SM22, and MYH11, while decreasing the expression of the synthetic marker osteopontin. EphrinB2/Fc treatment inhibited SMC migration, but not proliferation. In addition, overexpression of EphB4 increased mRNA expression of SMC contractile markers, while decreasing expression of the Apoptosis marker caspase-9.

Conclusions: EphB4 was present and functional in adult human venous SMCs. Stimulation of EphB4 increased expression of contractile SMC phenotypic markers and decreased SMC migration in vitro, functioning to retain the contractile phenotype of SMCs. EphB4 activation, therefore, recapitulates changes observed during vein graft adaptation to the arterial environment in vivo. EphB4 represents a new strategy to inhibit neointimal hyperplasia during vein graft adaption.

Keywords

EphB4; Vein graft; human; smooth muscle cell.

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