Abstract
Abstract only Natural ‘bioactive’ factors have the ability to attenuate atherogenesis in in vitro and in vivo models. The effects of cranberry on the expression of two inflammation‐linked enzymes, cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS), were examined in aortic smooth muscle (A7r5) cells in the absence/presence of tumour necrosis factor alpha (TNFα). Western blot analysis revealed that while cranberry did not affect base‐line protein expression of COX‐2, it did reduce base‐line levels of iNOS protein. Cranberry was able to effectively reduce the TNFα‐stimulated induction of both these enzymes. This reduction was observed after 6, 12, and 24 hours pre‐exposure to cranberry prior to exposure to TNFα, and after a 6 hour co‐incubation of cranberry with TNF. NFkB (a transcriptional regulator of COX‐2 and iNOS) expression was assessed in response to cranberry treatment. Base‐line cytosolic levels of the phosphorylated form of NFkB (p‐NFkB) were reduced following exposure to cranberry. Cranberry also reduced TNFα‐stimulated p‐NFkB levels. Taken together, these results suggest that cranberry may partly modulate the inflammatory response observed in atherosclerosis by affecting the expression of COX‐2 and iNOS, and that this modulation may occur through interaction with the NFkB transcription factor. The temporal/signal transduction mechanisms involved are being studied. [CIHR‐RPP, ACOA‐AIF‐2, UMassD‐Cranberry Research Program]