Basic Research in Cardiology

, Volume 100, Issue 1, pp 84–91

The angiotensin II type 1 receptor blocker valsartan attenuates graft vasculopathy

  • Tetsufumi Yamamoto
  • Masataka Sata
  • Daiju Fukuda
  • Shinichi Takamoto
ORIGINAL CONTRIBUTION

DOI: 10.1007/s00395-004-0489-0

Cite this article as:
Yamamoto, T., Sata, M., Fukuda, D. et al. Basic Res Cardiol (2005) 100: 84. doi:10.1007/s00395-004-0489-0

Abstract

Objective

Transplant arteriosclerosis remains the major cause of graft failure after cardiac transplantation. Here, we investigated the effects of the angiotensin II type 1 receptor blocker valsartan on the development of transplant arteriosclerosis in a murine model of cardiac transplantation.

Methods

Hearts from DBA/2 (H–2d) mice were heterotopically transplanted into B10.D2 (H–2d) mice. Recipients were treated with oral administration of valsartan (10 mg/kg/day) or vehicle.

Results

Morphometrical analysis of the cardiac allografts harvested at 30 days revealed that valsartan significantly reduced the development of coronary atherosclerosis (intima/media ratio: 0.39 ± 0.05 vs. 0.66 ± 0.08, P < 0.01). At two weeks after transplantation, there was no significant difference between the two groups in expression of adhesion molecules and cytokines. Valsartan significantly reduced the number of peripheral mononuclear cells that differentiated into smooth muscle–like cells in the presence of basic fibroblast growth factor and platelet–derived growth factor BB (18.0 ± 1.5 vs. 30.3 ± 4.4 cells/HPF, P = 0.01).

Conclusions

These results suggest that angiotensin II plays a role in the pathogenesis of transplant arteriosclerosis and that blockade of angiotensin II type 1 receptor might be effective as a prophylactic therapy for transplant arteriosclerosis along with conventional immunosuppressive drugs.

Key words

Transplantation arteriosclerosis angiotensin smooth muscle cell progenitor 

Copyright information

© Steinkopff Verlag 2004

Authors and Affiliations

  • Tetsufumi Yamamoto
    • 1
  • Masataka Sata
    • 2
    • 3
  • Daiju Fukuda
    • 2
  • Shinichi Takamoto
    • 1
  1. 1.Dept. of Cardiothoracic SurgeryUniversity of Tokyo Graduate School of MedicineTokyoJapan
  2. 2.Dept. of Cardiovascular MedicineUniversity of Tokyo Graduate School of MedicineTokyo 113-8655Japan
  3. 3.PRESTOJapan Science and Technology Agency KawaguchiSaitamaJapan

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