Activator protein-1 in carotid plaques is related to cerebrovascular symptoms and cholesteryl ester content.
BACKGROUND
Transcription factor activator protein-1 regulates genes involved in inflammation and repair. The aim of this study was to determine whether transcription factor activator protein-1 activity in carotid plaques is related to symptoms, lipid accumulation, or extracellular matrix composition.


METHODS
Twenty-eight atherosclerotic carotid plaques were removed by endarterectomy and divided into two groups based on the presence or absence of ipsilateral symptoms (<1 month ago). Activator protein-1 DNA binding activity was assessed, and subunit (c-Jun, JunD, JunB, c-Fos, FosB, Fra-1, Fra-2) protein levels analyzed by immunoblotting. Distribution of c-Jun in plaques was analyzed by immunohistochemistry.


RESULTS
Plaques associated with symptoms had increased activator protein-1 activity and increased expression of c-Jun and JunD, as compared to asymptomatic plaques. Fra-1 and Fra-2 were present in equal amounts in both groups, whereas JunB, FosB, and c-Fos were undetectable. Activator protein-1 activity correlated with cholesteryl ester and elastin in plaques and decreased with age. Activator protein-1 activity did not correlate with collagen, calcified tissue, or proteoglycan content.


CONCLUSIONS
Activator protein-1 is increased in plaques associated with symptoms. The correlation between activator protein-1 and cholesteryl esters suggests that high activator protein-1 is a marker of plaque vulnerability. Activator protein-1 expression can also reflect the activation of repair processes.
Gonçalves
Isabel
I
Department of Clinical Sciences, Clinical Research Center, Lund University, Malmö, Sweden. isabel.goncalves@med.lu.se
Stollenwerk
Maria M
MM
Lindholm
Marie W
MW
Dias
Nuno
N
Pedro
Luís M
LM
Fernandes
José Fernandes E
JF
Moses
Jonatan
J
Fredrikson
Gunilla Nordin
GN
Nilsson
Jan
J
Ares
Mikko P S
MP
D000368:Aged; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D021122:Protein Subunits; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*
D002788:Cholesterol Esters; D021122:Protein Subunits; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1