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Gewählte Publikation:

Oemar, BS; Werner, A; Garnier, JM; Do, DD; Godoy, N; Nauck, M; März, W; Rupp, J; Pech, M; Lüscher, TF.
Human connective tissue growth factor is expressed in advanced atherosclerotic lesions.
Circulation. 1997; 95(4):831-839 Doi: 10.1161/01.CIR.95.4.831 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
März Winfried
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Abstract:
BACKGROUND: Atherosclerosis affects certain but not all vascular beds of the human circulation. Its molecular mechanisms are only partially understood. Human connective tissue growth factor (hCTGF) is a novel cysteine-rich, secreted polypeptide. hCTGF is implicated in connective tissue formation, which may play an important role in atherosclerosis. METHODS AND RESULTS: By using a differential cloning technique, we isolated a cDNA clone from a human aorta cDNA library, which is identical to hCTGF. Northern analysis shows that hCTGF mRNA was expressed at 50- to 100-fold higher levels in atherosclerotic blood vessels compared with normal arteries. In vascular smooth muscle cells, high-level expression of hCTGF mRNA was induced by transforming growth factor-beta 1. Using in situ hybridization and immunohistochemistry, we found that all advanced atherosclerotic lesions of human carotid arteries (eight patients; mean age, 69; age range, 57 to 85 years) and femoral arteries (two patients; mean age, 71.5 years) that we tested expressed high levels of both hCTGF mRNA and protein. hCTGF expression was localized mainly to smooth muscle cells in the plaque lesions that are negative for proliferating cell nuclear antigen staining. In addition, some CD-31-positive endothelial cells of plaque vessels expressed high levels of hCTGF mRNA and protein. hCTGF-positive cells were found predominantly in areas with extracellular matrix accumulation and fibrosis. In contrast, in normal arteries, we were unable to detect either hCTGF mRNA or immunoreactive hCTGF protein. CONCLUSIONS: In the present study, we have shown for the first time that both hCTGF mRNA and protein are expressed in human arteries in vivo and that hCTGF may represent a novel factor expressed at high levels specifically in advanced lesions and may play a role in the development and progression of atherosclerosis.
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Adult -
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Arteries - metabolism
Arteriosclerosis - metabolism
Carotid Artery Diseases - metabolism
Cells, Cultured - metabolism
Cloning, Molecular - metabolism
Endarterectomy - metabolism
Female - metabolism
Gene Expression Regulation - metabolism
Gene Library - metabolism
Growth Substances - biosynthesis
Humans - biosynthesis
Immediate-Early Proteins - biosynthesis
In Situ Hybridization - biosynthesis
Intercellular Signaling Peptides and Proteins - biosynthesis
Male - biosynthesis
Middle Aged - biosynthesis
Mitogens - biosynthesis
Molecular Sequence Data - biosynthesis
Muscle, Smooth, Vascular - metabolism
RNA, Messenger - biosynthesis
Transcription, Genetic - biosynthesis

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arteriosclerosis
carotid arteries
endothelium
growth substances
stenosis
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