Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves
Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves
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DOI：
10.1016/j.jtcvs.2010.08.064
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发表时间：
2011-01-01
影响因子：
6
通讯作者：
Byrne, Guerard W.
中科院分区：
文献类型：
--
作者：
McGregor, Christopher G. A.;Carpentier, Alain;Byrne, Guerard W.
目的：人类和东半球灵长类动物对半乳糖-α-1，3-半乳糖-β-1，4-N-乙酰氨基葡萄糖(α-Gal)的抗体水平较高。商业上可用的猪和牛来源的生物人工心脏瓣膜保留了Gal抗原，尽管目前的加工技术。缺乏GAL的猪会消除这种异种抗原。本研究采用标准的猪心包皮下植入模型，检测人抗Gal抗体结合对野生型和Gal缺陷型戊二醛固定的猪心包钙化的影响。方法：用凝集素Griffia Simicifolia IB4染色检测α-Gal的表达。将来自Gal阳性和Gal缺乏猪的戊二醛固定的心包盘植入12日龄Wistar大鼠和1.5 kg体重的兔体内，并用亲和纯化的人抗Gal抗体预先标记和不标记。结果：在野生型猪心包中检测到α-Gal抗原，而在Gal缺陷型猪心包中未检测到α-Gal抗原。经人抗Gal抗体标记的野生型视盘的钙化程度显著高于未标记的野生型标本(平均+/-标准误差分别为111+/-8.4和74+/-9.6 mg/g；P=0.01)。在存在抗Gal抗体的情况下，野生型与GTKO猪心包相比，检测到的钙化水平显著更高(分别为111+/-8.4和55+/-11.8 mg/g；P=0.005)。抗Gal抗体(51+/-9.1 mg/g和55+/-11.8 mg/g)对Gal缺陷型心包钙化无明显影响。结论：在该模型中，抗Gal抗体可促进野生型而非Gal缺陷型戊二醛固定心包的钙化。这项研究表明，所有患者体内存在的预先形成的抗Gal抗体可能有助于目前使用的生物瓣膜的钙化。缺乏GAL的猪可能成为新的、潜在的抗钙生物人工心脏瓣膜的首选来源。(《胸心外科杂志》2011；141：269-75)
Objectives: Human subjects and Old World primates have high levels of antibody to galactose-alpha-1,3 galactose beta-1,4-N-acetylglucosamine (alpha-Gal). Commercially available bioprosthetic heart valves of porcine and bovine origin retain the Gal antigen despite current processing techniques. Gal-deficient pigs eliminate this xenoantigen. This study tests whether binding of human anti-Gal antibody effects calcification of wild-type and Gal-deficient glutaraldehyde-fixed porcine pericardium by using a standard subcutaneous implant model.Methods: Expression of alpha-Gal was characterized by lectin Griffonia simplicifolia-IB4 staining. Glutaraldehyde-fixed pericardial disks from Gal-positive and Gal-deficient pigs were implanted into 12-day-old Wistar rats and 1.5-kg rabbits with and without prelabeling with affinity-purified human anti-Gal antibody. Calcification of the implants was determined after 3 weeks by using inductively coupled plasma spectroscopy.Results: The alpha-Gal antigen was detected in wild-type but not Gal-deficient porcine pericardium. Wild-type disks prelabeled with human anti-Gal antibody exhibited significantly greater calcification compared with that seen in antibody-free wild-type samples (mean +/- standard error of the mean: 111 +/- 8.4 and 74 +/- 9.6 mg/g, respectively; P = .01). In the presence of anti-Gal antibody, a significantly greater level of calcification was detected in wild-type compared with GTKO porcine pericardium (111 +/- 8.4 and 55 +/- 11.8 mg/g, respectively; P = .005). Calcification of Gal-deficient pericardium was not affected by the presence of anti-Gal antibody (51 +/- 9.1 and 55 +/- 11.8 mg/g).Conclusions: In this model anti-Gal antibody accelerates calcification of wild-type but not Gal-deficient glutaraldehyde- fixed pericardium. This study suggests that preformed anti-Gal antibody present in all patientsmight contribute to calcification of currently used bioprosthetic heart valves. Gal-deficient pigsmight become the preferred source for new, potentially calcium-resistant bioprosthetic heart valves. (J Thorac Cardiovasc Surg 2011;141:269-75)