TY - JOUR
T1 - AKT2 Promotes Bone Marrow Cell-Mediated Aortic Protection in Mice
AU - Zou, Sili
AU - Ren, Pingping
AU - Zhang, Lin
AU - Azares, Alon R.
AU - Zhang, Sui
AU - Coselli, Joseph S.
AU - Shen, Ying H.
AU - LeMaire, Scott A.
N1 - Publisher Copyright:
© 2016 The Society of Thoracic Surgeons.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.athoracsur.2016.01.026
DO - 10.1016/j.athoracsur.2016.01.026
M3 - Article
C2 - 27090732
AN - SCOPUS:84963680081
SN - 0003-4975
VL - 101
SP - 2085
EP - 2096
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 6
ER -