Related Experiment Videos
Human connective tissue growth factor is expressed in advanced atherosclerotic lesions
B S Oemar1, A Werner, J M Garnier
1Division of Cardiology, University Hospital Bern, Switzerland. OEMAR@UBACLU.UNIBAS.CH
Insights
Human connective tissue growth factor (hCTGF) is highly expressed in atherosclerotic arteries, not normal ones. This finding suggests hCTGF may play a key role in atherosclerosis development and progression.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pathology
Background:
- Atherosclerosis pathogenesis involves complex molecular mechanisms across different vascular beds.
- Human connective tissue growth factor (hCTGF) is a secreted polypeptide linked to connective tissue formation.
- hCTGF's role in atherosclerosis, a condition involving connective tissue changes, is under investigation.
Purpose of the Study:
- To investigate the expression and localization of hCTGF in human atherosclerotic arteries.
- To determine if hCTGF is differentially expressed in diseased versus normal vasculature.
- To explore the potential role of hCTGF in the molecular mechanisms of atherosclerosis.
Main Methods:
- Differential cloning to isolate hCTGF cDNA from a human aorta library.
- Northern blot analysis to quantify hCTGF mRNA levels in normal and atherosclerotic arteries.
- In situ hybridization and immunohistochemistry to localize hCTGF mRNA and protein in human carotid and femoral arteries.
- Analysis of hCTGF expression in relation to specific cell types (smooth muscle cells, endothelial cells) and extracellular matrix components within atherosclerotic plaques.
Main Results:
- hCTGF mRNA was found at 50- to 100-fold higher levels in atherosclerotic blood vessels compared to normal arteries.
- High-level hCTGF mRNA expression in vascular smooth muscle cells was induced by transforming growth factor-beta 1.
- Advanced atherosclerotic lesions in human carotid and femoral arteries showed high levels of both hCTGF mRNA and protein.
- hCTGF expression was primarily localized to smooth muscle cells and some endothelial cells within plaque lesions, particularly in areas of fibrosis and extracellular matrix accumulation.
- Neither hCTGF mRNA nor protein was detected in normal arteries.
Conclusions:
- This study demonstrates for the first time the in vivo expression of hCTGF mRNA and protein in human arteries.
- hCTGF is significantly upregulated in advanced atherosclerotic lesions.
- hCTGF may represent a novel molecular factor contributing to the development and progression of atherosclerosis.
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.