|Nie, Lin - TUFTS/HNRCA|
Submitted to: American Aging Association
Publication Type: Abstract Only
Publication Acceptance Date: June 2, 2006
Publication Date: June 2, 2006
Citation: Nie, L., Wise, M., Meydani, M. 2006. Mechanism by Which Avenanthramide-C, a Polyphenol of Oats, Blocks Cell Cycle Progression in Vascular Smooth Muscle Cells. AGE. 28(1):54-55. Technical Abstract: Atherosclerosis is a chronic inflammatory disease which manifests its clinical symptom at a later age. Abnormal growth of smooth muscle cell (SMC) contributes to the initiation and progression of this chronic disease; therefore, nutritional inhibition of the proliferation of SMC is considered to be important for the prevention of atherogenesis or reduction the risk this aging related disease. Avenanthramides (Avn) are unique polyphenols present in oats. We have reported that Avn-c, one of the major forms of Avn with the most antioxidant activity, inhibited the serum-induced cell proliferation of SMC. In the present study, we investigated the mechanism by which Avn-c inhibits proliferation of SMC. Rat embryonic aortic smooth muscle cell line A10 was used in this study. Flow cytometry analysis revealed that treatment of A10 cell with 80 uM Avn-c arrested the cell cycle in G1 phase as indicated by an increase in the G1 cell population (from 49.7percent to 66.9percent) and a decrease in the number of cells in S phase (from 40percent to 25.7percent). This cell cycle arrest was associated with a decreased in the phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1-S transition in the cell cycle. The inhibition of pRb phosphorylation with Avn-c was accompanied by a decrease in cyclin D1 expression and an increase in cyclin-dependent kinase inhibitor p21cip1 expression, without significant changes in p27kip1 expression. Avn-c treatment also increased p53 protein expression level and its stability, which could account for the increase of p21cip1 expression. Our results demonstrate that Avn-c inhibits SMC proliferation and arrests the cell cycle at G1 phase by up-regulating p53-p21cip1 pathway and by inhibiting pRB phosphorylation. This inhibitory effect of Avn-c on SMC proliferation is another indication of the potential health benefit of oats consumption for the prevention of cardiovascular disease. Supported by 58-1950-9-001 CRIS.