Connective tissue growth factor is overexpressed in complicated atherosclerotic plaques and induces mononuclear cell chemotaxis in vitro.
OBJECTIVE
Atherosclerotic blood vessels overexpress connective tissue growth factor (CTGF) mRNA, but the role of CTGF in atherosclerosis remains controversial. To assess the hypothesis that CTGF is involved in atherosclerotic plaque progression, we investigated CTGF protein expression and distribution in the different types of plaque morphology.


RESULTS
Serial cross-sections of 45 human carotid plaques were immunohistochemically analyzed for the presence of CTGF protein, neovascularization (von Willebrand factor), macrophages (CD68), and T cells (CD3). The lesions were categorized according to American Heart Association (AHA) classification as fibrous (type IV and V) or complicated plaques (type VI). The levels of CTGF were significantly higher in complicated compared with fibrous plaques (P=0.002). CTGF accumulated particularly in the rupture-prone plaque shoulder and in the areas of neovascularization or infiltration with inflammatory cells. Macrophage-like cells stained positive for CTGF protein in plaques. Subsequent in vitro studies showed that although monocyte-derived macrophages do not produce CTGF on stimulation with transforming growth factor-beta, lipopolysaccharide, or thrombin, they take it up from culture medium. Furthermore, CTGF induces mononuclear cell chemotaxis in a dose-dependent manner.


CONCLUSIONS
CTGF protein is significantly increased in complicated compared with fibrous plaques and may enhance monocyte migration into atherosclerotic lesions, thus contributing to atherogenesis.
Cicha
Iwona
I
Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany. Iwona_Cicha@yahoo.com
Yilmaz
Atilla
A
Klein
Michael
M
Raithel
Dieter
D
Brigstock
David R
DR
Daniel
Werner G
WG
Goppelt-Struebe
Margarete
M
Garlichs
Christoph D
CD
D000368:Aged; D002340:Carotid Artery Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D055513:Connective Tissue Growth Factor; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism; D014657:Vasculitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor