| Extracellular
Matrix-Mediated Control of Smooth Muscle Cell Growth and Migration
by a Combination of Ascorbic Acid, Lysine, Proline and Catechins
V. Ivanov, S. Ivanova, M.W. Roomi, A. Niedzwiecki, M. Rath, Matthias
Rath BV, Santa Clara, CA
Presented at: 75th European Atherosclerotic
Society Congress, Prague, Czech Republic, April 23-26, 2005.
Published in: Atherosclerosis, vol 6, issue
1, 2005, p.18.
Abstract
Objective
Extracellular matrix (ECM) function and structure are severely
compromised at atherosclerotic lesion sites, contributing to initiation
and progression of the disease. We investigated whether ECM biological
properties would be beneficially affected by exposure to nutrients
essential for collagen synthesis and post-translational modification.
Methods
- Confluent layers of human aortic smooth muscle cells (SMC)
grown on collagen substrate were cultured in the presence of
the tested compounds for seven to ten days.
- Pre-treated cells were removed from the ECM surface by differential
treatment and replaced with secondary innocent SMC cultures.
- Secondary SMC growth rate and invasiveness were assayed in
standard growth medium.
- ECM protein composition was assayed immunochemically.
Results
- ECM produced in the presence of ascorbic acid significantly
reduced SMC proliferation as compared to the untreated control.
- Plant-derived phenolic extracts expressed different degrees
of SMC growth inhibition when present during ECM production.
- A combination of selected nutrients had a greater effect
than did individual components.
- The ECM deposited by SMC in the presence of ascorbate, lysine,
proline and green tea catechins inhibited SMC migration rate
up to 70%
- ECM integrity and strength were significantly improved by
SMC treatment with NM. This was demonstrated by increased collagen
type IV to I ratio and by increased chondroitin sulfate to heparan
sulfate ratio.
Conclusion
ECM produced under conditions of chronic essential nutrient deficiency
can support pro-atherosclerotic SMC behavior.
The combination of nutrients can counteract these adverse effects
stronger than individual components.
Comment:
Under conditions of chronic essential nutrient deficiency,
the extracellular matrix (ECM) produced can support the development
of atherosclerotic lesions. We investigated the effect of
nutrients essential for collagen synthesis on ECM biological
properties: SMC proliferation, invasiveness and migration,
and collagen type ratios. The ECM deposited in the presence
of a mixture of nutrients (ascorbate, lysine, proline, and
green tea extract) had improved strength and integrity (increased
collagen IV: I and chondroitin sulfate: heparan) and significantly
inhibited SMC migration up to 70%. These results are important
as they indicate that proper nutrient supplementation can
prevent the formation of atherosclerotic lesions. |
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