Genetic disruption of angiotensin II type 1a receptor improves long-term survival of mice with chronic severe aortic regurgitation
Genetic disruption of angiotensin II type 1a receptor improves long-term survival of mice with chronic severe aortic regurgitation
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DOI：
10.1253/circj.71.1310
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发表时间：
2007-08-01
影响因子：
3.3
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
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作者：
Nakanishi, Michio;Harada, Masaki;Nakao, Kazuwa
背景主动脉瓣反流（AR）引起左心室（LV）容量超负荷，导致进行性LV扩张和功能障碍。在本研究中，它是检查是否血管紧张素B I型受体（ATI）的封锁可以改善生存的情况下，慢性严重AR。方法和结果AR是通过穿刺野生型（WT）和AT 1a基因敲除（KO）小鼠的主动脉瓣诱导。手术后存活4周的小鼠被认为是慢性严重AR的模型，并随访50周（WT. n=29; KO，n=31）。术后4周进行的基线测量显示两种基因型的LV腔和功能相似。这些情况在两种基因型中逐渐恶化，但基线后16周，KO小鼠显示出比WT小鼠显著更少的LV扩张，肥大和间质纤维化。KO小鼠心脏B型利钠肽和I型胶原mRNA表达低于WT小鼠。KO小鼠的50周死亡率（45.2%）明显低于WT小鼠（86.2%），尸检结果表明，较低的死亡率归因于充血性心力衰竭的发生率较低。结论在慢性严重AR的情况下，AT 1的阻滞可减弱LV扩张、肥大和纤维化的进展，从而减轻心力衰竭并提高长期生存率。
Background Aortic regurgitation (AR) causes left ventricular (LV) volume overload, leading to progressive LV dilatation and dysfunction. In the present study it was examined whether blockade of angiotensin B type I receptor (ATI) could improve survival in cases of chronic severe AR.Methods and Results AR was induced by puncturing the aortic valves of wild-type (WT) and AT1a knockout (KO) mice. Mice that survived for 4 weeks after the operation were deemed to be a model of chronic severe AR and were followed up for 50 weeks (WT. n=29; KO, n=31). Baseline measurements made 4 weeks after surgery showed similar LV cavity and function in both genotypes. These conditions progressively worsened in both genotypes, but 16 weeks after baseline, KO mice showed significantly less LV dilatation, hypertrophy and interstitial fibrosis than WT mice. Cardiac mRNA expression of B-type natriuretic peptide and type I collagen was lower in KO than WT mice. The 50-week mortality rate was significantly lower among KO (45.2%) than WT (86.2%) mice, and postmortem findings indicated that the lower mortality was attributable to a lower incidence of congestive heart failure.Conclusions In cases of chronic severe AR, blockade of AT1 attenuates the progression of LV dilatation, hypertrophy and fibrosis, thereby mitigating heart failure and improving long-term survival.