Axl modulates immune activation of smooth muscle cells in vein graft remodeling.
The pathophysiological mechanisms of the immune activation of smooth muscle cells are not well understood. Increased expression of Axl, a receptor tyrosine kinase, was recently found in arteries from patients after coronary bypass grafts. In the present study, we hypothesized that Axl-dependent immune activation of smooth muscle cells regulates vein graft remodeling. We observed a twofold decrease in intimal thickening after vascular and systemic depletion of Axl in vein grafts. Local depletion of Axl had the greatest effect on immune activation, whereas systemic deletion of Axl reduced intima due to an increase in apoptosis in vein grafts. Primary smooth muscle cells isolated from Axl knockout mice had reduced proinflammatory responses by prevention of the STAT1 pathway. The absence of Axl increased suppressor of cytokine signaling (SOCS)1 expression in smooth muscle cells, a major inhibitory protein for STAT1. Ultrasound imaging suggested that vascular depletion of Axl reduced vein graft stiffness. Axl expression determined the STAT1-SOCS1 balance in vein graft intima and progression of the remodeling. The results of this investigation demonstrate that Axl promotes STAT1 signaling via inhibition of SOCS1 in activated smooth muscle cells in vein graft remodeling.
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York; and.
Sri N
SN
Batchu
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York; and.
Jixiang
J
Xia
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York; and.
Kyung Ae
KA
Ko
Department of Electrical and Computer Engineering, University of Rochester and Hajim School of Engineering and Applied Sciences, Rochester, New York; and.
Marvin M
MM
Doyley
University of Texas MD Anderson Cancer Center, Houston, Texas.
Jun-Ichi
J
Abe
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York; and.
Craig N
CN
Morrell
Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York; and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, New York; Slava_Korshunov@urmc.rochester.edu.
Vyacheslav A
VA
Korshunov
D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000276:immunology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000276:immunology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism; D066253:Vascular Remodeling / Q000276:immunology*; D059289:Vascular Stiffness / Q000276:immunology*; D014682:Vena Cava, Inferior / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D000094963:Axl Receptor Tyrosine Kinase
D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; C494080:Stat1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722290:AXL receptor tyrosine kinase, mouse
Axl; inflammation; smooth muscle cell; vascular remodeling