Connective tissue growth factor is associated with a stable atherosclerotic plaque phenotype and is involved in plaque stabilization after stroke.
OBJECTIVE
Carotid plaques remodel toward a more stable phenotype after stroke, but not after TIA. Connective tissue growth factor (CTGF) is involved in extracellular matrix production and is expressed in atherosclerotic plaques. We studied the role of CTGF in plaque remodeling after stroke and TIA.


METHODS
Atherosclerotic plaques from carotid endarterectomy of asymptomatic patients (n = 16) and patients who experienced stroke (n = 15) or TIA (n = 33) were analyzed for CTGF levels, markers of plaque stability (collagen, smooth muscle cells, macrophage content, and lipid core), and levels of matrix metalloproteinase (MMP)-8, MMP-9, IL-4, IL-5, and IL-10.


RESULTS
CTGF levels were higher in stroke patients compared to TIA patients. Plaques with a high level of CTGF revealed more collagen and smooth muscle cell content, whereas macrophage content and lipid core size were not different. The amount of CTGF was negatively associated with MMP-8 and MMP-9 activity and showed a positive correlation with the anti-inflammatory cytokines IL-4, IL-5, and IL-10.


CONCLUSIONS
CTGF levels are associated with a more stable plaque phenotype. CTGF is increased in plaques after stroke compared to TIA, suggesting a role for CTGF in plaque stabilization after stroke.
Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. a.vink@umuctrecht.nl
Jan Willem
JW
Leeuwis
Tri Q
TQ
Nguyen
Maarten G J
MG
Theunissen
Wouter
W
Peeters
Roel
R
Goldschmeding
Gerard
G
Pasterkamp
Aryan
A
Vink
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology*; D012307:Risk Factors; D020521:Stroke / Q000378:metabolism* / Q000473:pathology*
D015415:Biomarkers; D007378:Interleukins; D055513:Connective Tissue Growth Factor; D003094:Collagen; D020782:Matrix Metalloproteinases