Vadim Ivanov, Svetlana Ivanova, M. Waheed Roomi, Aleksandra Niedzwiecki, Matthias Rath.
Dr Rath Research Institute, Santa Clara, California, USA
76th Congress of the European Atherosclerosis Society; Helsinki, Finland; June 10-13, 2007
Atherosclerosis Supplements, volume 8, issue 1, June 2007, page 163, poster #P020-598
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.
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.
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.
We conclude that plant-derived nutrients can inhibit monocyte retention inside arterial wall by specific modulation of ECM composition.
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.