Copyright © 2005, European Society of Cardiology
Small interfering RNA knocks down heat shock factor-1 (HSF-1) and exacerbates pro-inflammatory activation of NF-
B and AP-1 in vascular smooth muscle cells
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5
* Corresponding author. Tel.: +1 902 494 3343; fax: +1 902 494 1212. Email address: wcurrie{at}dal.ca
Objectives: Heat shock and elevated expression of heat shock proteins suppress activation of the pro-inflammatory transcription factor NF-
B. We hypothesized that knocking down the expression of heat shock factor-1 (HSF-1) with RNAi technology would exacerbate angiotensin (Ang) II-induced inflammatory injury in vascular smooth muscle cells (VSMC).
Methods: Rat aorta A10 cells and human intestinal smooth muscle cells were grown without transfection or with transfection with HSF-1 small interfering RNA (siRNA), or negative control siRNA. Cells were stimulated with Ang II (100 nM) to activate the NF-B signaling pathway.
Results: HSF-1 siRNA significantly knocked down HSF-1 expression, and one of the downstream heat shock proteins (Hsp), Hsp27, in both cells lines. HSF-1 siRNA also affected cells stressed with heat shock or Ang II treatment. Ang II induced activation of NF-B and AP-1 in untransfected VSMCs, however, Ang II induced significantly higher activities of these pro-inflammatory transcription factors in HSF-1 siRNA transfected cells. Control siRNA had no apparent effect on HSF-1 and Hsp27 expression and Ang II-induced NF-B and AP-1 activation.
Conclusions: These data indicate that the knock down of HSF-1 exacerbates Ang II-induced inflammation in VSMCs, and suggests that heat shock proteins protect against inflammatory injury by suppression of pro-inflammatory transcription factors such as NF-B and AP-1.
KEYWORDS HSF-1; Heat shock proteins; Angiotensin II; NF-B; AP-1; Inflammation
Time for primary review 21 days
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