Expression of gax, a growth arrest homeobox gene, is rapidly down-regulated in the rat carotid artery during the proliferative response to balloon injury.
gax is a recently described homeobox gene whose expression in the adult is largely confined to cardiovascular tissues, gax has been shown to be rapidly down-regulated in cultured vascular smooth muscle cells (VSMC) upon stimulation by serum or platelet-derived growth factor. The temporal profile of gax expression in vitro matches that of two families of growth arrest genes: the gas genes and the gadd genes. All of these genes are expressed at their highest levels in quiescent cells and are down-regulated following mitogen activation. Here we report that gax is also down-regulated in vivo in the vascular wall in response to endothelial denudation by balloon angioplasty. The reduction in steady state levels of gax mRNA is transient and occurs with a similar time course to that seen in vitro. The down-regulation of gax in response to balloon injury mirrors the up-regulation seen in a number of early response genes such as c-myc and c-fos. This report is the first to document the in vivo expression of a growth arrest gene which regulates proliferation of vascular smooth muscle cells. In addition, in contrast with previous reports which have demonstrated up-regulation of several genes following balloon injury and/or angioplasty, the present report demonstrates the down-regulation of a regulatory gene within hours of balloon injury. The characteristics of gax suggest it may be required to maintain the gene expression of proteins in VSMC that are associated with the nonproliferative or contractile phenotype in smooth muscle cells.
Weir
L
L
Department of Medicine (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135.
Chen
D
D
Pastore
C
C
Isner
J M
JM
Walsh
K
K
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000235:genetics*; D017931:DNA Primers; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D016762:Genes, fos; D016259:Genes, myc; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D007700:Kinetics; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
D017931:DNA Primers; D018398:Homeodomain Proteins; C081336:Meox2 protein, rat; D009124:Muscle Proteins; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases