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Endothelial cell effect on smooth muscle cell collagen synthesis
R J Powell1, J Hydowski, O Frank
1Section of Vascular Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
The Journal of Surgical Research
|April 1, 1997
Summary
Endothelial cells (ECs) significantly inhibit smooth muscle cell (SMC) collagen synthesis and type I collagen gene expression. This inhibition is not mediated by TGF-beta 1 and is influenced by the extracellular matrix.
Area of Science:
- Vascular Biology
- Cellular and Molecular Medicine
- Biochemistry
Background:
- Extracellular matrix (ECM) is a major component of intimal hyperplastic lesions.
- Understanding cell-cell interactions in vascular remodeling is crucial for disease understanding.
Purpose of the Study:
- To investigate whether endothelial cells (ECs) inhibit smooth muscle cell (SMC) collagen synthesis.
- To determine the role of TGF-beta 1 in EC-mediated regulation of SMC collagen production.
- To assess the impact of different culture substrates on EC-SMC interactions and collagen synthesis.
Main Methods:
- Bovine aortic SMCs were cultured alone or co-cultured with ECs on various substrates (plastic, type I collagen, matrigel, fibronectin, type IV collagen).
- Collagen synthesis was quantified using [3H]proline incorporation and expressed as trichloroacetic acid-precipitable counts per microgram of SMC DNA.
- SMC type I collagen gene expression was analyzed via Northern blot.
- Experiments included the use of neutralizing antibodies to TGF-beta 1 and plasmin inhibitors (aprotinin).
Main Results:
- ECs significantly inhibited SMC collagen synthesis by 40% and type I collagen gene expression by 60% compared to SMCs cultured alone.
- TGF-beta 1 neutralizing antibody and aprotinin did not affect collagen synthesis in SMCs cultured alone.
- Culture substrates modulated SMC collagen synthesis, with fibronectin and type I collagen increasing synthesis, while matrigel and type IV collagen decreased it.
- ECs reduced SMC collagen synthesis on type I collagen and matrigel, but fibronectin abolished this inhibitory effect.
Conclusions:
- Endothelial cells effectively inhibit smooth muscle cell collagen synthesis and downregulate type I collagen gene expression.
- Transforming growth factor-beta 1 (TGF-beta 1) does not appear to mediate this EC-induced inhibition.
- The composition of the extracellular matrix significantly influences SMC collagen synthesis and the ability of ECs to modulate this process.