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Endothelial cell-conditioned medium downregulates smooth muscle contractile protein expression
S M Vernon1, M J Campos, T Haystead
1Department of Medicine (Cardiology), University of Virginia School of Medicine, Charlottesville 22908, USA.
The American Journal of Physiology
|February 1, 1997
Summary
Endothelial cells release factors that promote smooth muscle cell (SMC) proliferation and dedifferentiation. These factors, found in endothelial cell-conditioned medium (ECCM), reduce the expression of key contractile proteins in SMC.
Area of Science:
- Vascular Biology
- Cellular Signaling
- Atherosclerosis Research
Background:
- Smooth muscle cells (SMC) in atherosclerotic lesions undergo proliferation and phenotypic changes.
- The role of the vascular endothelium in modulating SMC behavior is not fully understood.
Purpose of the Study:
- To investigate the impact of endothelial cell-conditioned medium (ECCM) on the growth and differentiation of vascular SMC.
- To identify potential factors produced by endothelial cells that influence SMC behavior.
Main Methods:
- Cultured rat aortic endothelial cells were used to generate ECCM.
- ECCM was applied to rat aortic SMC to assess effects on [3H]thymidine incorporation and contractile protein synthesis.
- Characterization of ECCM activity involved heat, trypsinization, molecular weight, and heparin-binding assays.
- Specific growth factors and their inhibitors were tested for their effects.
Main Results:
- ECCM significantly increased SMC proliferation (ninefold increase in [3H]thymidine incorporation).
- ECCM downregulated the synthesis of smooth muscle-specific myosin heavy chain and alpha-actin.
- The observed effects were independent of platelet-derived growth factor (PDGF)-BB, PDGF-AB, or PDGF beta-receptor.
- None of the tested individual growth factors (PDGF-BB, PDGF-AA, FGF, endothelin-1, TGF-beta) replicated the ECCM effects.
Conclusions:
- Cultured endothelial cells secrete factor(s) that promote SMC proliferation.
- These endothelial-derived factors also downregulate contractile protein expression, leading to SMC dedifferentiation.
- This process may contribute to the pathogenesis of atherosclerotic lesions.