Haptoglobin phenotype correlates with development of cardiac transplant vasculopathy
Haptoglobin phenotype correlates with development of cardiac transplant vasculopathy
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DOI：
10.1016/s1053-2498(03)00061-5
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发表时间：
2004-01-01
影响因子：
8.9
通讯作者：
Keevil, B
中科院分区：
文献类型：
--
作者：
Densem, CG;Wassel, J;Keevil, B
目的：本研究的目的是探讨接触红蛋白表型变异与心脏移植血管病变发展之间的关系。背景：冠状动脉病变的发展决定心脏移植术后的长期生存。血清触珠蛋白水平与非移植动脉粥样硬化相关。此外，通过游离血红蛋白结合，触珠蛋白影响自由基的形成、前列腺素的合成和血管生成。人类中存在三种触珠蛋白表型，它们在数量和质量上都存在差异。方法：冠状动脉移植术后常规监测血管造影诊断冠心病。将血红蛋白（10%）添加到受体血浆中形成触珠蛋白-血红蛋白复合物。样品等分液应用于酸性血红蛋白板，电泳分离。通过将电泳模式与已建立的标准进行比较来识别表型。采用聚乙二醇（PEG）增强沉淀法免疫比浊技术测定触珠蛋白浓度。结果：93例患者独立研究。1-1型占20.4%，2-1型占41.9%，2-2型占37.6%。1-1受体的Haptoglobin水平最高（2.1 +/- 0.58 g/l），而2-1和2-2受体的Haptoglobin水平分别为1.78 +/- 0.88 g/l和1.3 +/- 0.81 g/l （p = 0.001）。触珠蛋白表型与血管病变的发生有显著相关性；2-1表型受体更容易发生血管造影疾病（p = 0.0084）。经单因素分析，3组间无差异。多因素分析确定了血管病变发生的3个危险因素：供体年龄（危险比1.056[95%可信区间1.02 ~ 1.094],p = 0.0023）；移植前受者体重指数（风险比1.116[95%可信区间1.015 ~ 1.23],p = 0.024）和珠蛋白表型（风险比2.725[95%可信区间1.031 ~ 7.19],p = 0.012）。结论：珠蛋白通过表型依赖机制与冠状动脉病变的发生相关。这一发现进一步加深了我们对这种疾病的了解，开辟了新的研究领域，并可能导致新的治疗方法。心肺移植[J]; 2004;23:43-49。
Objectives: The purpose of this study was to investigate the association between haptoglobin phenotypic variation and development of cardiac transplant vasculopathy.Background: The development of coronary vasculopathy determines long-term survival after cardiac transplantation. Serum haptoglobin levels are associated with non-transplant atherosclerosis. In addition, to free hemoglobin binding, haptoglobin influences free radical formation, prostaglandin synthesis and angiogenesis. Three phenotypes of haptoglobin exist in humans, which have both quantitative and qualitative differences.Methods: Coronary disease was diagnosed at post-transplant routine surveillance angiography. Hemoglobin (10%) was added to recipient plasma to form a haptoglobin-hemoglobin complex. Sample aliquots were applied to acid hemoglobin plates and electrophoretically separated. Phenotypes were recognized by comparing the electrophoretic pattern with that of established standards. Haptoglobin concentrations were measured using an immunoturbidimetric technique with polyethylene glycol (PEG)-enhanced precipitation.Results: Ninety-three patients were independently studied. Phenotype 1-1 was found in 20.4%, 2-1 in 41.9% and 2-2 in 37.6%. Haptoglobin levels were highest in 1-1 recipients (2.1 +/- 0.58 g/liter) compared with 1.78 +/- 0.88 g/liter and 1.3 +/- 0.81 g/liter in 2-1 and 2-2 individuals, respectively (p = 0.001). Haptoglobin phenotype was significantly related to the development of vasculopathy; recipients with a 2-1 phenotype were more likely to develop angiographic disease (p = 0.0084). No differences were found among the 3 groups according to univariate analysis. Multivariate analysis identified 3 risk factors for vasculopathy development: age of donor (hazard ratio 1.056 [95% confidence interval 1.02 to 1.094], p = 0.0023); pre-transplant recipient body mass index (hazard ratio 1.116 [95% confidence interval 1.015 to 1.23],p = 0.024), and haptoglobin phenotype (hazard ratio 2.725 [95% confidence interval 1.031 to 7.19], p = 0.012).Conclusions: Haptoglobin, through phenotype-dependent mechanisms, correlates with the development of coronary vasculopathy. This finding furthers our understanding of the disease, opens up new areas of research, and may lead to novel therapies. J Heart Lung Transplant 2004;23:43-49.