title: AKT2 Promotes Bone Marrow Cell-Mediated Aortic Protection in Mice.
abstract: BACKGROUND
  Insufficient aortic protection and repair may contribute to the development of aortic aneurysms and dissections (AAD). However, mechanisms of aortic protection and repair are poorly understood. We have shown that the multifunctional kinase AKT2 plays an important role in protecting the aortic wall. Here, we examined whether AKT2 protects against AAD by promoting bone marrow cell (BMC)-mediated aortic protection.
  
  
  METHODS
  Irradiated wild-type mice received green fluorescent protein-expressing BMCs from wild-type mice or Akt2(-/-) mice, followed by challenge with angiotensin II (1000 ng/kg/min) infusion for 4 weeks. We compared BMC recruitment, aortic destruction, and AAD development between groups. The direct effects of wild-type and Akt2(-/-) BMCs on smooth muscle cell survival were examined in coculture experiments.
  
  
  RESULTS
  After angiotensin II infusion, no (0 of 14) wild-type BMC recipients had AAD; in contrast, 64% (9 of 14) of Akt2(-/-) BMC recipients had AAD (p = 0.002) with severe aortic destruction. Compared with aortas from challenged wild-type BMC recipients, aortas from challenged Akt2(-/-) BMC recipients showed significantly less BMC recruitment, NG2 (neuron-glial antigen 2) progenitor activation, and FSP1 (fibroblast-specific protein 1) fibroblast activation. In addition, aortas from challenged Akt2(-/-) BMC recipients showed increased apoptosis and inflammation. In coculture experiments, wild-type but not Akt2(-/-) BMCs prevented smooth muscle cells from undergoing oxidative stress-induced apoptosis.
  
  
  CONCLUSIONS
  After aortic challenge, BMCs are recruited to the aortic wall and provide protection by activating progenitors and fibroblasts and by promoting aortic cell survival. Our findings indicate that AKT2 is involved in these processes and that defects in this pathway may promote progressive degeneration during AAD development.
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Vascular Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Sili
authors.initials: S
authors.lastname: Zou
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas.
authors.forename: Pingping
authors.initials: P
authors.lastname: Ren
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Stem Cell Research, Texas Heart Institute, Houston, Texas.
authors.forename: Alon R
authors.initials: AR
authors.lastname: Azares
authors.affiliation: Stem Cell Research, Texas Heart Institute, Houston, Texas.
authors.forename: Sui
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, CHI St. Luke's Health-Baylor St. Luke's Medical Center, Houston, Texas.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Coselli
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas.
authors.forename: Ying H
authors.initials: YH
authors.lastname: Shen
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Cardiovascular Research Institute, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, CHI St. Luke's Health-Baylor St. Luke's Medical Center, Houston, Texas. Electronic address: slemaire@bcm.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: LeMaire
mesh_terms: D000784:Aortic Dissection / Q000201:enzymology / Q000503:physiopathology*; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D001014:Aortic Aneurysm / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000201:enzymology / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000473:pathology; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology; D020286:Pericytes / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011828:Radiation Chimera; D015398:Signal Transduction; D013234:Stem Cells / Q000201:enzymology / Q000473:pathology
chemical_list: D000804:Angiotensin II; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt