Lipid-mediated inflammation and degeneration of bioprosthetic heart valves
Lipid-mediated inflammation and degeneration of bioprosthetic heart valves
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DOI：
10.1111/j.1365-2362.2009.02132.x
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发表时间：
2009-06-01
影响因子：
5.5
通讯作者：
Mathieu, P.
中科院分区：
文献类型：
--
作者：
Shetty, R.;Pibarot, P.;Mathieu, P.
生物瓣膜的耐久性受到结构性瓣膜退化（SVD）的限制，导致生物瓣膜（BP）狭窄或返流。我们假设脂质介导的炎症机制参与了BP的SVD。18例Freestyle无支架BP瓣膜在植入后平均5.9 +/- 3年因SVD接受了手术，并通过免疫组织化学和透射电镜（TEM）进行了分析。患者平均年龄为65 +/- 8岁，其中11例男性和7例女性患者。18个BP中有2个存在肉眼可见钙化，而其他瓣膜存在极轻微或无肉眼可见钙化。16例BP中存在导致返流的连合处撕裂。免疫组化显示13例BP的纤维层中存在氧化低密度脂蛋白（ox-LDL）和糖胺聚糖。ox-LDL区域被共表达清道夫受体CD 36和金属蛋白酶-9（MMP-9）的巨噬细胞（CD 68（+））浸润。酶谱显示MMP-9的活性形式存在于降解的BP中。EM研究显示存在以泡沫细胞和碎片胶原为特征的载脂细胞。未植入的对照BP（n = 4）在瓣叶内无脂质积聚、炎性细胞浸润或MMP 9表达，这些结果支持脂质介导的炎症机制可能导致BP SVD的观点。这些结果表明，使用行为或药物干预来改变动脉粥样硬化风险因素可能有助于降低SVD的发生率。
The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs.Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM).The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets.These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.