title: Increased antioxidant defense mechanism in human adventitia-derived progenitor cells is associated with therapeutic benefit in ischemia.
abstract: OBJECTIVE
  Vascular wall-resident progenitor cells hold great promise for cardiovascular regenerative therapy. This study evaluates the impact of oxidative stress on the viability and functionality of adventitia-derived progenitor cells (APCs) from vein remnants of coronary artery bypass graft (CABG) surgery. We also investigated the antioxidant enzymes implicated in the resistance of APCs to oxidative stress-induced damage and the effect of interfering with one of them, the extracellular superoxide dismutase (EC-SOD/SOD3), on APC therapeutic action in a model of peripheral ischemia.
  
  
  RESULTS
  After exposure to hydrogen peroxide, APCs undergo apoptosis to a smaller extent than endothelial cells (ECs). This was attributed to up-regulation of antioxidant enzymes, especially SODs and catalase. Pharmacological inhibition of SODs increases reactive oxygen species (ROS) levels in APCs and impairs their survival. Likewise, APC differentiation results in SOD down-regulation and ROS-induced apoptosis. Oxidative stress increases APC migratory activity, while being inhibitory for ECs. In addition, oxidative stress does not impair APC capacity to promote angiogenesis in vitro. In a mouse limb ischemia model, an injection of naïve APCs, but not SOD3-silenced APCs, helps perfusion recovery and neovascularization, thus underlining the importance of this soluble isoform in protection from ischemia.
  
  
  METHODS
  This study newly demonstrates that APCs are endowed with enhanced detoxifier and antioxidant systems and that SOD3 plays an important role in their therapeutic activity in ischemia.
  
  
  CONCLUSIONS
  APCs from vein remnants of CABG patients express antioxidant defense mechanisms, which enable them to resist stress. These properties highlight the potential of APCs in cardiovascular regenerative medicine.
authors: 1 Expermental Cardiovascular Medicine, School of Clinical Sciences, University of Bristol , Bristol, United Kingdom .
authors: Dominga
authors: D
authors: Iacobazzi
authors: Giuseppe
authors: G
authors: Mangialardi
authors: Miriam
authors: M
authors: Gubernator
authors: Manuela
authors: M
authors: Hofner
authors: Matthias
authors: M
authors: Wielscher
authors: Klemens
authors: K
authors: Vierlinger
authors: Carlotta
authors: C
authors: Reni
authors: Atsuhiko
authors: A
authors: Oikawa
authors: Gaia
authors: G
authors: Spinetti
authors: Rosa
authors: R
authors: Vono
authors: Elena
authors: E
authors: Sangalli
authors: Monica
authors: M
authors: Montagnani
authors: Paolo
authors: P
authors: Madeddu
mesh_terms: D063194:Adventitia / Q000166:cytology*; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005121:Extremities / Q000098:blood supply; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D016130:Immunophenotyping; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D000975:Antioxidants; D017382:Reactive Oxygen Species; C441642:SOD3 protein, human; D013482:Superoxide Dismutase