Antiproliferative gene BTG1 is highly expressed in apoptotic cells in macrophage-rich areas of advanced lesions in Watanabe heritable hyperlipidemic rabbit and human.
In the present study, the expression and potential role of the highly conserved antiproliferative gene BTG1 in the process of apoptosis as it occurs in atherosclerotic lesions was examined. In situ hybridization and immunodetection studies demonstrated that BTG1 localized to specific macrophage-rich regions of lesions in both Watanabe heritable hyperlipidemic rabbits and humans. In addition, the spatial distribution of BTG1 mRNA was shown to colocalize not only with macrophage-rich regions but also to cells that exhibited changes consistent with apoptosis, such as DNA fragmentation and nuclear condensation. In vitro studies demonstrated that forced overexpression of BTG1 induced a 3-fold increase in apoptosis in NIH/3T3 cells. Furthermore, significantly increased expression of BTG1 mRNA resulted from lipid loading of human monocyte-derived macrophages in vitro. The process of increasing lipid content in macrophages is frequently associated with decreased macrophage viability. Taken together, these data underscore a potentially important role for BTG1 in regulating the cellularity of advanced atherosclerotic lesions.
Dupont Merck Research Laboratories, Experimental Station, Wilmington, Delaware 19880, USA.
M H
MH
Corjay
M A
MA
Kearney
D A
DA
Munzer
S M
SM
Diamond
J K
JK
Stoltenborg
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D001583:Benzoxazoles; D002455:Cell Division; D002461:Cell Line, Transformed; D053938:DNA Fragmentation; D005456:Fluorescent Dyes; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D011806:Quinolinium Compounds; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection
D001583:Benzoxazoles; C489552:Btg1 protein, mouse; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D011806:Quinolinium Compounds; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; C075296:1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium; C074086:BTG1 protein, human