Connective tissue growth factor induction in a pressure-overloaded heart ameliorated by the angiotensin II type 1 receptor blocker olmesartan
Connective tissue growth factor induction in a pressure-overloaded heart ameliorated by the angiotensin II type 1 receptor blocker olmesartan
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DOI：
10.1038/hr.2010.189
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发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Ninomiya, Yoshifumi
中科院分区：
文献类型：
--
作者：
Iwamoto, Mutsumi;Hirohata, Satoshi;Ninomiya, Yoshifumi
结缔组织生长因子（CTGF）是一种分泌性蛋白质，调节纤维化。我们假设CTGF在压力超负荷（PO）心脏中被诱导，并且阻断血管紧张素II 1型受体将减少CTGF表达。因此，我们给药奥美沙坦，并比较其与其他抗高血压药物在PO心脏的作用。在大鼠PO模型中测定CTGF诱导，并连续给予奥美沙坦、肼苯哒嗪或盐水。评价奥美沙坦对CTGF诱导、心肌细胞肥大和纤维化的影响。还在CTGF和转化生长因子-β 1（TGF-β 1）输注大鼠中检查了奥美沙坦对心脏功能的影响。主动脉缩窄术后3天，PO心脏中CTGF增加，并明显分布于血管周围纤维化区域。28天后，奥美沙坦和肼苯哒嗪组的血压没有显著差异，但奥美沙坦治疗减少了PO心脏中CTGF的分布。奥美沙坦与显著降低的心肌细胞肥大指数相关（奥美沙坦组为4.77 ± 0.48，生理盐水组为6.05 ± 1.45，P
Connective tissue growth factor (CTGF) is a secreted protein that regulates fibrosis. We hypothesized that CTGF is induced in a pressure-overloaded (PO) heart and that blocking the angiotensin II type 1 receptor would reduce CTGF expression. Accordingly, we administered olmesartan and compared its effects with other antihypertensive drugs in a PO heart. CTGF induction was determined in a rat PO model, and olmesartan, hydralazine or saline was continuously administered. The effects of olmesartan on CTGF induction, myocyte hypertrophy and fibrosis were evaluated. The effect of olmesartan on cardiac function was also examined in CTGF-and transforming growth factor-beta 1 (TGF-beta 1)-infused rats. CTGF was increased in the PO heart 3 days after aortic banding and was markedly distributed around the perivascular fibrotic area. After 28 days, blood pressure was not significantly different in the olmesartan and hydralazine groups, but olmesartan treatment reduced CTGF distribution in PO hearts. Olmesartan was associated with a significantly reduced myocyte hypertrophy index (4.77 +/- 0.48 for olmesartan and 6.05 +/- 1.45 for saline, P