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Updated: Aug 9, 2026
Mouse Models for Graft Arteriosclerosis
Published on: May 14, 2013
The angiotensin II type 1 receptor blocker valsartan attenuates graft vasculopathy
Tetsufumi Yamamoto1, Masataka Sata, Daiju Fukuda
1Dept. of Cardiothoracic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Insights
Valsartan, an angiotensin II type 1 receptor blocker, significantly reduced transplant arteriosclerosis in a mouse heart transplant model. This suggests valsartan could be a prophylactic therapy for preventing graft failure.
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Pharmacology
Background:
- Transplant arteriosclerosis is a primary cause of cardiac allograft failure.
- Understanding the mechanisms driving transplant arteriosclerosis is crucial for improving long-term graft survival.
Purpose of the Study:
- To investigate the efficacy of valsartan, an angiotensin II type 1 receptor blocker, in mitigating transplant arteriosclerosis.
- To explore the role of angiotensin II in the pathogenesis of transplant arteriosclerosis.
Main Methods:
- A murine model of heterotopic cardiac transplantation was utilized.
- Recipients received daily oral administration of valsartan (10 mg/kg/day) or a vehicle control.
Main Results:
- Valsartan significantly reduced coronary atherosclerosis development (intima/media ratio).
- No significant difference in adhesion molecules or cytokines was observed at two weeks.
- Valsartan decreased the differentiation of peripheral mononuclear cells into smooth muscle-like cells.
Conclusions:
- Angiotensin II is implicated in the pathogenesis of transplant arteriosclerosis.
- Blockade of the angiotensin II type 1 receptor with valsartan shows potential as a prophylactic therapy.
- Valsartan may be a valuable adjunct to conventional immunosuppressive strategies in cardiac transplantation.
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-2(d)) mice were heterotopically transplanted into B10.D2 (H-2(d)) 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.
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