Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits
Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits
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DOI：
10.1038/bjp.2008.122
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发表时间：
2008-06-01
影响因子：
7.3
通讯作者：
Tardif, J-C
中科院分区：
文献类型：
--
作者：
Busseuil, D.;Shi, Y.;Tardif, J-C
背景和目的：主动脉瓣狭窄（AVS）是最常见的心脏瓣膜病，标准的治疗方法仍然是心脏直视手术瓣膜置换术。我们实验研究的目的是确定是否载脂蛋白A-I（ApoA-I）模拟肽输注可以诱导AVS的消退。实验方法：15只新西兰白色雄性家兔接受富含胆固醇的饮食和维生素D（2），直到超声心动图检测到明显的AVS。然后停止富集饮食以模拟降胆固醇治疗，并将动物随机分配接受盐水（对照组，n=8）或ApoA-I模拟肽（治疗组，n=7），每周三次，持续2周。主要结果：治疗组主动脉瓣面积在治疗14天后显著增加了25%（P=0.012）。同样，治疗组的主动脉瓣厚度降低了21%，而对照组无变化（P=0.0006）。组织学分析显示，与对照组相比，治疗组的瓣叶和主动脉窦基底病变程度较小（P=0.032）。治疗也减少了钙化，所揭示的损失的正相关关系，观察到在对照组（r=0.87，P=0.004）之间的钙化面积和主动脉瓣thicken.Conclusions和影响：输注ApoA-I模拟肽导致实验性AVS的回归。这些积极的结果证明进一步测试高密度脂蛋白（HDL）为基础的治疗与主动脉瓣狭窄患者。主动脉瓣狭窄的消退，如果安全实现，可能会改变这种疾病的临床治疗。
Background and purpose: Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS.Experimental approach: Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D(2) until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed.Key results: Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness.Conclusions and implications: Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease.