The angiotensin II type 1 receptor blocker valsartan attenuates graft vasculopathy
The angiotensin II type 1 receptor blocker valsartan attenuates graft vasculopathy
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DOI：
10.1007/s00395-004-0489-0
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发表时间：
2004
影响因子：
9.5
通讯作者：
Tetsufumi Yamamoto;M. Sata;D. Fukuda;S. Takamoto
中科院分区：
文献类型：
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作者：
Tetsufumi Yamamoto;M. Sata;D. Fukuda;S. Takamoto
移植动脉硬化仍然是心脏移植术后移植物衰竭的主要原因，尽管最近免疫抑制治疗的进展已显着提高了受体的短期存活率。我们研究了血管紧张素Ⅱ 1型受体（AT 1 R）阻断剂坎地沙坦对小鼠心脏移植模型移植动脉硬化的影响。材料与方法将DBA/2（H-2d）小鼠的心脏异位移植到B10.D2（H-2d）小鼠。接受者经口给予坎地沙坦（每天1 mg/kg）或溶媒。移植后第14天和第30天对移植物进行分析，结果显示：坎地沙坦组冠状动脉粥样硬化程度明显减轻（内膜/中膜比值：0.86 ± 0.09比0.57 ± 0.10，P < 0.05），但对30天的实质排斥反应程度无影响。14 d时粘附分子和细胞因子的表达无显著差异。坎地沙坦可显著减少在碱性成纤维细胞生长因子和血小板衍生生长因子BB存在下，外周血单个核细胞向平滑肌样细胞分化的数量（27.1 ± 3.1 vs17.3 ± 1.8 cells/HPF，P < 0.05）。阻断AT 1 R可能与常规免疫抑制药物一起沿着有效地作为移植动脉硬化的预防性治疗。
OBJECTIVETransplant arteriosclerosis remains the major cause of graft failure after cardiac transplantation, although recent progress in immunosuppressive therapy has dramatically improved short-term survival of recipient. We investigated the effects of the angiotensin II type 1 receptor (AT1R) blocker candesartan on the development of transplant arteriosclerosis in a murine model of cardiac transplantation.MATERIALS AND METHODSHearts from DBA/2 (H-2d) mice were heterotopically transplanted into B10.D2 (H-2d) mice. Recipients were treated with oral administration of candesartan (1 mg/kg per day) or vehicle. Allografts were analyzed at 14 or 30 days after transplantation.RESULTSCandesartan significantly reduced the development of coronary arteriosclerosis (intima/media ratio: 0.86 ± 0.09 versus 0.57 ± 0.10, P < 0.05), without affecting the degree of parenchymal rejection at 30 days. There was no significant difference in the expression of adhesion molecules and cytokines at 14 days. Candesartan 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 (27.1 ± 3.1 versus 17.3 ± 1.8 cells/HPF, P < 0.05).CONCLUSIONSAngiotensin II may play a role in the pathogenesis of transplant arteriosclerosis. Blockade of AT1R might be effective as a prophylactic therapy for transplant arteriosclerosis along with conventional immunosuppressive drugs.