title: Treatment with telmisartan attenuates graft arteriosclerosis in murine cardiac allografts.
abstract: BACKGROUND
  Chronic rejection remains the most prominent cause of graft failure after transplantation. Recently, it was reported that telmisartan can function as a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) in addition to a blocker of angiotensin II receptor. We investigated the effect of telmisartan on chronic rejection.
  
  
  METHODS
  Hearts from Bm12 mice were transplanted into C57BL/6 mice (Class II mismatch), and allografts were harvested at 8 weeks after transplantation. Recipient mice were fed either control chow or chow containing telmisartan (10 mg/kg/day) from 1 day before transplantation. Proliferation assays of smooth muscle cells (SMCs), which were isolated from the aorta of B/6 mice, was performed.
  
  
  RESULTS
  Although severe neo-intimal hyperplasia developed in allografts from control mice fed chow (luminal occlusion 70.9 +/- 6.1%), neo-intimal hyperplasia was significantly attenuated in allografts from mice fed chow containing telmisartan (30.0 +/- 10%, p < 0.001). Expression of interferon (IFN)-gamma and interleukin (IL)-15 mRNAs and matrix metalloproteinase (MMP)-2 in allografts was significantly lower in telmisartan-treated mice than in control mice. Proliferation of smooth muscle cells (SMCs) in response to fetal bovine serum was suppressed significantly by telmisartan (10 micromol/liter). The PPARgamma antagonist blocked telmisartan-induced suppression of SMC proliferation.
  
  
  CONCLUSIONS
  Telmisartan attenuates SMC proliferation via PPARgamma activity and suppresses neo-intimal hyperplasia after transplantation. Telmisartan may be useful for suppressing chronic allograft rejection.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan. kosuge.cvm@tmd.ac.jp
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kosuge
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Go
authors.initials: G
authors.lastname: Haraguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maejima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saiki
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003324:Coronary Artery Disease / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology*; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists*; D000077333:Telmisartan; D014184:Transplantation, Homologous; D017540:Tunica Media / Q000276:immunology / Q000473:pathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D016207:Cytokines; D047495:PPAR gamma; D000077333:Telmisartan