title: Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells.
abstract: BACKGROUND
  Activation of nuclear factor-kappaB (NF-kappaB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50).
  
  
  RESULTS
  Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque material of 52 patients), SMC from the human coronary media (HCMSMC), human endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6 hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-kappaB1 p50.
  
  
  CONCLUSIONS
  The data point out that differences exist in the NF-kappaB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.
authors.affiliation: Department of Internal Medicine II - Cardiology, University of Ulm, Robert-Kochstrasse 8, D-89081 Ulm, Germany. rainer.voisard@medizin.uni-ulm.de
authors.forename: R
authors.initials: R
authors.lastname: Voisard
authors.forename: N
authors.initials: N
authors.lastname: Huber
authors.forename: R
authors.initials: R
authors.lastname: Baur
authors.forename: M
authors.initials: M
authors.lastname: Susa
authors.forename: O
authors.initials: O
authors.lastname: Ickrath
authors.forename: A
authors.initials: A
authors.lastname: Both
authors.forename: W
authors.initials: W
authors.lastname: Koenig
authors.forename: V
authors.initials: V
authors.lastname: Hombach