Involvement of Serum Response Factor (SRF) in Acrolein‐mediated activation of NF[kappa]B in vascular Smooth Muscle Cells (VSMC)

Modulation of inflammatory signaling has been elucidated in different disease models including vascular biology. Acrolein‐induced toxicity in vasculature has been linked to inflammatory process involving activation of NFkB. SRF, a transcription factor, has been shown to regulate cell development, differentiation and proliferation. SRF‐induced proliferation involves molecule such as ERK1/2 and CD36. In this study we explored the hypothesis that acrolein‐induced NFkB activation requires SRF and involves CD36 and ERK1/2 signaling mechanism. VSMCs were exposed to 0.5 μg/ml of acrolein in presence or absence of 10 nM QNZ (NFkB inhibitor), 300 nM CCG‐1423 (SRF inhibitor), and 50 μM 98059 (ERK1/2 inhibitor) in the media. There is a ~2‐fold increase in SRF protein expression in acrolein treated cells compared to the control. This increase is associated with a significant potentiation of NFkB activity (188%; p<0.01) which is attenuated in presence of CCG‐1423 (52%; p<0.05). These data suggests that SRF is an intermediate in acrolein‐induced activation of NFkB. Changes in NFkB activity was not reflected in NFkB protein expression. Similarly, both ERK1/2 and CD36 protein expression was unchanged in acrolein treated cells and NFkB activity or protein expression was not altered in presence of any of their inhibitor. From this study we suggest that SRF is required in acrolein‐induced activation of NFkB in VSMC.