TY - JOUR
T1 - Expression of the FAST-1 transcription factor in coronary artery transplant vasculopathy and activated vascular smooth muscle cells
AU - Kelemen, Sheri F.
AU - Eisen, Howard J.
AU - Autieri, Michael V.
PY - 2005/3
Y1 - 2005/3
N2 - Background: The activation of vascular smooth muscle cells (VSMCs) causes most of the obliterative vasculopathy responsible for solid-organ allograft failure. Identification of genes expressed in activated VSMCs may provide clues to the pathogenesis and progression of cardiac allograft vasculopathy (CAV). Methods: We performed cDNA micro-array analysis of mRNA isolated from a healthy human coronary artery, from a coronary artery from a patient with CAV, and from quiescent and stimulated cultured human coronary artery VSMCs. Western blot analysis and immunohistochemistry verified fork-head activin signal transdurcer 1 (FAST-1) expression. Results: Fold-change analysis determined that increased expression of a transcription factor involved in transforming growth factor beta (TGF-β) signaling, FAST-1, was induced in arteries with CAV and in activated VSMCs, compared with normal and unstimulated cells. Western blotting confirmed increased FAST-1 expression in arteries with CAV vs normal arteries and arteries from failing hearts and confirmed increased expression in cultured VSMCs stimulated with a variety of cytokines. Immunohistochemical analysis determined that FAST-1 expression localized to neo-intimal VSMCs in rejecting arteries. In cultured VSMCs, FAST-1 immunolocalizes to the nucleus after TGF-β stimulation. Conclusions: These results demonstrate differential expression of the FAST-1 gene in the VSMC response to inflammatory stimuli. Considering the significant role of TGF-β in vascular fibroproliferative diseases, this work suggests that FAST-1 may participate in the VSMC response to injury and may represent a potential molecular target for modulating the progression of CAV.
AB - Background: The activation of vascular smooth muscle cells (VSMCs) causes most of the obliterative vasculopathy responsible for solid-organ allograft failure. Identification of genes expressed in activated VSMCs may provide clues to the pathogenesis and progression of cardiac allograft vasculopathy (CAV). Methods: We performed cDNA micro-array analysis of mRNA isolated from a healthy human coronary artery, from a coronary artery from a patient with CAV, and from quiescent and stimulated cultured human coronary artery VSMCs. Western blot analysis and immunohistochemistry verified fork-head activin signal transdurcer 1 (FAST-1) expression. Results: Fold-change analysis determined that increased expression of a transcription factor involved in transforming growth factor beta (TGF-β) signaling, FAST-1, was induced in arteries with CAV and in activated VSMCs, compared with normal and unstimulated cells. Western blotting confirmed increased FAST-1 expression in arteries with CAV vs normal arteries and arteries from failing hearts and confirmed increased expression in cultured VSMCs stimulated with a variety of cytokines. Immunohistochemical analysis determined that FAST-1 expression localized to neo-intimal VSMCs in rejecting arteries. In cultured VSMCs, FAST-1 immunolocalizes to the nucleus after TGF-β stimulation. Conclusions: These results demonstrate differential expression of the FAST-1 gene in the VSMC response to inflammatory stimuli. Considering the significant role of TGF-β in vascular fibroproliferative diseases, this work suggests that FAST-1 may participate in the VSMC response to injury and may represent a potential molecular target for modulating the progression of CAV.
KW - Blotting, Western
KW - Cells, Cultured
KW - Coronary Vessels/metabolism
KW - DNA-Binding Proteins/metabolism
KW - Forkhead Transcription Factors
KW - Heart Diseases/metabolism
KW - Heart Transplantation
KW - Humans
KW - Immunohistochemistry
KW - Muscle, Smooth, Vascular/metabolism
KW - Oligonucleotide Array Sequence Analysis
KW - Signal Transduction/physiology
KW - Transcription Factors/metabolism
UR - http://www.scopus.com/inward/record.url?scp=14644435060&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000227463800002&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.healun.2004.01.015
DO - 10.1016/j.healun.2004.01.015
M3 - Article
C2 - 15737749
SN - 1053-2498
VL - 24
SP - 246
EP - 250
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 3
ER -