Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, Republic of Korea.
Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, Republic of Korea.
J Thorac Cardiovasc Surg. 2019 Sep;158(3):731-741.e1. doi: 10.1016/j.jtcvs.2018.12.042. Epub 2019 Jan 10.
There are pathophysiologic similarities between calcification and atherosclerosis because both are the product of an active inflammatory process. The aim of the study was to examine the effects of statin treatment on calcification in commercially available bioprosthetic heart valves.
Twenty Sprague-Dawley rats were fed a high-fat diet to induce hypercholesterolemia during 4 weeks. They were randomly divided into 2 groups according to statin intake (control, n = 10: high-fat diet/statin; n = 10: high-fat diet with statin). Four commercially available tissue valve (Magna Perimount, Carpentier-Edwards, Irvine, Calif; Hancock, Medtronic, Minneapolis, Minn; Mitroflow, LivaNova, London, England; and Trifecta, St Jude Medical, St Paul, Minn) cusp samples (total 320) were implanted in rat dorsal subcutis at 4 weeks. After implantation, rosuvastatin was administered daily to the statin group. The cusps were explanted at 12 weeks, and calcium levels were determined by atomic absorption spectroscopy. Western blotting, histologic, and immunohistochemical analyses were conducted to identify the anticalcification mechanism of the statin.
The mean calcium level in the control group was significantly higher than in the statin group (P < .01) for all tissue valves (Magna Perimount: 2.67 ± 0.26 mg/g vs 1.31 ± 0.40 mg/g; Hancock: 2.70 ± 0.57 mg/g vs 1.53 ± 0.34 mg/g; Mitroflow: 2.39 ± 0.71 mg/g vs 1.26 ± 0.38 mg/g; Trifecta: 2.54 ± 0.42 mg/g vs 1.63 ± 0.72 mg/g). Inflammatory cell infiltration and interleukin-6 and bone morphogenetic protein 2 expressions were significantly reduced in the statin group.
Statin treatment significantly attenuated bioprosthetic heart valve calcification associated with decreasing the levels of interleukin-6 and bone morphogenetic protein 2. Thus, statin treatment might be helpful for the longevity of bioprosthetic heart valves.
钙化和动脉粥样硬化之间存在病理生理学相似性，因为两者都是活跃炎症过程的产物。本研究旨在研究他汀类药物治疗对商业上可获得的生物瓣钙化的影响。
20 只 Sprague-Dawley 大鼠接受高脂饮食喂养 4 周，以诱导高胆固醇血症。根据他汀类药物摄入情况（对照组，n=10：高脂饮食/他汀类药物；n=10：高脂饮食加他汀类药物）将它们随机分为 2 组。将 4 种商业上可获得的组织瓣（Magna Perimount、Carpentier-Edwards、Irvine，加利福尼亚州；Hancock、Medtronic、明尼苏达州明尼阿波利斯；Mitroflow、LivaNova、英国伦敦；和 Trifecta、St Jude Medical、明尼苏达州圣保罗）的瓣叶样本（共 320 个）在大鼠背部皮下植入 4 周。植入后，给他汀组每天给予瑞舒伐他汀。12 周后取出瓣叶，原子吸收光谱法测定钙含量。进行 Western 印迹、组织学和免疫组织化学分析，以确定他汀类药物的抗钙化机制。
对照组的平均钙水平明显高于他汀组（P<.01），所有组织瓣均如此（Magna Perimount：2.67±0.26mg/g 与 1.31±0.40mg/g；Hancock：2.70±0.57mg/g 与 1.53±0.34mg/g；Mitroflow：2.39±0.71mg/g 与 1.26±0.38mg/g；Trifecta：2.54±0.42mg/g 与 1.63±0.72mg/g）。他汀组炎症细胞浸润和白细胞介素-6 和骨形态发生蛋白 2 的表达明显减少。
他汀类药物治疗显著减轻了与白细胞介素-6 和骨形态发生蛋白 2 水平降低相关的生物瓣钙化。因此，他汀类药物治疗可能有助于延长生物瓣的寿命。
