Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada.
Cardiovasc Pathol. 2011 Mar-Apr;20(2):84-92. doi: 10.1016/j.carpath.2010.01.004. Epub 2010 Feb 18.
Aortic valve sclerosis (AVS) is a common inflammatory heart valve disease prevalent in the population over the age of 65 years. Several published clinical and animal studies have examined the ability of statin treatment to modify disease progression. Clinical trials yielded conflicting results, and animal studies examined the effects of statins prior to the onset of disease. Our study assessed the effect of dietary modification and/or statin treatment on established aortic valve disease in a rabbit model of AVS to examine the tissue response to therapy.
Aortic valve sclerosis was induced in male New Zealand White rabbits by dietary cholesterol supplementation. Rabbits were followed over 2.5 years, with the introduction of statins and/or dietary changes for the second half of the study. At end point, valve function was examined by magnetic resonance imaging. Excised aortic valve cusp tissue was surveyed for thickness, lipid accumulation, protein deposition, calcification, and cellular infiltration.
By 15 months, cholesterol-fed valves exhibited thickening due to significant lipid content, macrophage infiltration, and osteopontin expression. By 30 months, the untreated disease had progressed to include elevated collagen deposition, lymphocyte invasion, and calcification. With treatment, however, the valve cusps exhibited significant pathological changes including diminished immune cell infiltration and osteopontin expression. Unfortunately, lipid was retained and calcification persisted in all treated valves.
In established AVS, the cellular response to statin therapy does not result in full regression of the sclerotic process.
主动脉瓣硬化（AVS）是一种常见的炎症性心脏瓣膜病，常见于 65 岁以上的人群。有几项已发表的临床和动物研究探讨了他汀类药物治疗对疾病进展的影响。临床试验得出了相互矛盾的结果，动物研究则在疾病发生前观察了他汀类药物的作用。我们的研究评估了饮食改变和/或他汀类药物治疗对 AVS 兔模型中已确立的主动脉瓣疾病的影响，以研究组织对治疗的反应。
通过饮食胆固醇补充剂在雄性新西兰白兔中诱导主动脉瓣硬化。在 2.5 年的随访期间，在研究的后半段引入他汀类药物和/或饮食改变。在终点，通过磁共振成像检查瓣膜功能。对取出的主动脉瓣瓣叶组织进行厚度、脂质积累、蛋白沉积、钙化和细胞浸润的调查。
15 个月时，胆固醇喂养的瓣膜由于显著的脂质含量、巨噬细胞浸润和骨桥蛋白表达而出现增厚。30 个月时，未经治疗的疾病进展为包括胶原沉积增加、淋巴细胞浸润和钙化。然而，经治疗后，瓣膜瓣叶出现了明显的病理变化，包括免疫细胞浸润和骨桥蛋白表达减少。不幸的是，所有治疗瓣膜中仍存在脂质蓄积和钙化。
在已确立的 AVS 中，他汀类药物治疗的细胞反应并未导致硬化过程的完全消退。
