title: Telmisartan prevents VCAM-1 induction and monocytic cell adhesion to endothelium exposed to non-uniform shear stress and TNF-α.
abstract: BACKGROUND
  Atherosclerotic plaques develop at arterial regions subjected to non-uniform shear stress, and are initiated by increased leukocyte-endothelial interactions. Here we applied the in vitro model of arterial bifurcations to investigate whether telmisartan, an anti-inflammatory angiotensin II receptor blocker with PPAR-gamma activating ability, prevents monocyte recruitment by endothelium.
  
  
  METHODS
  Human umbilical vein endothelial cells (ECs) were exposed to 18 h non-uniform shear stress in bifurcating flow-through slides, followed by 2 h stimulation with 2.5 ng/mL TNF-alpha. During flow, cells were treated with telmisartan. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Adherent THP-1 monocytes were quantified by light microscopy. Endothelial protein expression was determined by immunofluorescence.
  
  
  RESULTS
  Non-uniform shear stress in combination with TNF-alpha dramatically induced monocytic cell recruitment by endothelial cells. In cells treated with telmisartan (0.5-2.5 μmol/L) during exposure to non-uniform shear stress, dose-dependent inhibition of monocytic cell adhesion was observed, with about 45% reduction at 1 μmol/L. This effect was mediated by a significant reduction of endothelial VCAM-1 expression. On the contrary, the induction of E-selectin by TNF-alpha in ECs exposed to non-uniform shear stress was not affected by telmisartan. The inhibitory effect of telmisartan on monocytic cell recruitment and VCAM-1 induction was prevented in the presence of the PPAR-gamma antagonist GW9662.
  
  
  CONCLUSIONS
  Treatment with telmisartan decreases the TNF-α-induced recruitment of monocytic cells and endothelial expression of VCAM-1 in regions of non-uniform shear stress in vitro. This mechanism can contribute to the beneficial pleiotropic effects of telmisartan in atherosclerosis-prone arterial regions.
authors.affiliation: Department of Cardiology and Angiology, University of Erlangen-Nuremberg, Erlangen, Germany. Iwona Cicha@yahoo.com
authors.forename: Iwona
authors.initials: I
authors.lastname: Cicha
authors.forename: Katharina
authors.initials: K
authors.lastname: Urschel
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D013314:Stress, Mechanical; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000077333:Telmisartan