Cranberry (Vaccinium macrocarpon) extract inhibits matrix metalloproteinase expression in aortic smooth muscle cells by affecting key cell signaling pathways (934.1)

Abstract

A whole cranberry (Vaccinium macrocarpon) extract was shown to inhibit matrix metalloproteinase (MMP‐2 /MMP‐9) activity (assessed by zymography)in A7R5 aortic smooth muscle cells in vitro. Cranberry extract [CE] decreased cellular viability ~10% post 6 hours of treatment. Treatment of A7R5 cells with 100 ug/mL cranberry extract for 6 hours resulted in increased expression of TIMP‐1 & TIMP‐2 protein levels [inhibitors of MMPs] and decreased protein expression levels of EMMPRIN [an activator of MMPs]. In response to CE treatment, increased expression of JNK‐1, JNK‐2, pJNK‐1, pJNK‐2 & p38 protein levels occurred. No change in ERK‐1, ERK‐2 and pERK‐1 protein levels (assessed by Western blot analyses) occurred in response to cranberry treatment for 6 hours. However, a decrease in p‐p38 and in p‐ERK‐2 protein expression levels was noted in response to CE treatment.Treatment of A7R5 cells with CE (for 6 hours) also resulted in no apparent change in either AKT, pAKT, P‐I‐3 kinase p85 or p110 protein level expression. Treatment of A7R5 cells with CE (100 ug/mL) for 6 hours resulted in inhibition of FAK & p‐FAK protein expression levels . These results suggest that a whole cranberry extract has the ability to inhibit the expression of MMP‐2/‐9 activity in A7R5 aortic smooth muscle cells and suggests that this occurs via alterations in the expression of key protein modulators of MMPs’ expression and also involves changes in signal transduction pathways. (Canadian Institutes of Health Research [CIHR], P.E.I. Health Research Program, The Cranberry Institute ([Wisconsin Board ] funded).