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Plant-Derived Nutrients
Inhibit Monocyte Retention By Extracellular Matrix Produced By
Aortic Smooth Muscle and Endothelial Cells
Vadim Ivanov, Svetlana Ivanova, M. Waheed Roomi,
Aleksandra Niedzwiecki, Matthias Rath.
Dr Rath Research Institute, Santa Clara, California, USA
Presented at: 76th Congress
of the European Atherosclerosis Society; Helsinki, Finland; June
10-13, 2007
Published in: Atherosclerosis
Supplements, volume 8, issue 1, June 2007, page 163, poster #P020-598
Abstract
Introduction:
Monocyte retention within arterial wall is an important step in
initiation and progression of atherosclerosis. Compromised function
and structure of extracellular matrix (ECM) at lesion sites contribute
to this process.
Objective:
We investigated whether ECM biological properties would be beneficially
affected by exposure to plant-derived nutrients.
Materials and Methods:
Confluent layers of human aortic smooth muscle (AoSMC) and endothelial
(AoEC) cells were cultured in the presence of tested nutrients
and resulted ECM was exposed by differential treatment. Attachment
of human monocytic U937 cells to ECM was evaluated by fluorescent
assay. ECM proteins and glycosaminoglycans were analyzed by immunoenzyme
assay.
Results:
Among candidates tested ascorbic acid, quercetin, epigallocatechin
gallate and asiatic acid demonstrated the most pronounced effects
when tested individually and, especially, as a mixture. Monocyte
attachment to ECM produced under supplementation with the nutrient
mixture was reduced in a dose-dependent manner. Based on IC50
values, the inhibitory activity of nutrient mixture was two-fold
higher toward AoEC as compared to AoSMC. This difference was accompanied
by different patterns of nutrient-induced changes in ECM composition.
Monocyte attachment to AoEC-derived ECM positively correlated
with ECM enrichment in collagen type IV, followed by fibronectin,
collagen types III and I and elastin. Chondroitin sulfate content
was a strong negative correlate. Monocyte retention by AoSMC-derived
ECM positively correlated with collagen types III and I, followed
by laminin, heparan sulfate and fibronectin. Hyaluronic acid expression
was the strongest negative correlate.
Conclusion:
We conclude that plant-derived nutrients can inhibit monocyte
retention inside arterial wall by specific modulation of ECM composition.
Comment:
Compromised extracellular matrix (ECM) function and structure
at lesion sites contribute to monocyte retention within the
vascular wall and lead to the initiation and progression of
atherosclerosis. We investigated whether ECM biological properties
would be beneficially affected by exposure to plant-derived
nutrients. Of the nutrients tested, ascorbic acid, quercetin,
epigallocatechin gallate and asiatic acid demonstrated the
most pronounced effects individually, which was enhanced when
nutrients were combined. Monocyte attachment to ECM produced
under supplementation with the nutrient mixture was reduced
in a dose-dependent manner, with inhibition of moncyte attachment
greater with AoEC than AoSMC. The different patterns of AoEC-
and AoSMC-derived ECM attachment to monocytes were correlated
with nutrient-induced changes in the ECM composition. These
results are significant as they indicate that plant-derived
nutrients affect ECM composition and inhibit monocyte retention,
and thus would be beneficial in preventing progression of
atherosclerosis. |
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