Acquired hyperhomocysteinemia in heart transplant recipients.
Acquired hyperhomocysteinemia in heart transplant recipients.
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DOI：
10.1093/clinchem/44.11.2238
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发表时间：
1998-11
影响因子：
9.3
通讯作者：
D. Jacobsen
中科院分区：
文献类型：
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作者：
D. Jacobsen
高同型半胱氨酸血症的病因和临床意义正在深入研究中。尽管非遗传（1）和遗传（2）（3）（4）因素影响血浆同型半胱氨酸浓度，但通常在冠状动脉疾病、脑血管疾病、外周血管疾病和终末期肾病患者中发现的中度至中度高同型半胱氨酸血症（15-50 μmol/L）的病因尚不清楚。原因可能是多方面的，既涉及后天因素，也涉及遗传因素。有强有力的证据表明，高同型半胱氨酸血症是心血管疾病的独立风险因素（1）（5）（6）（7），但也有相互矛盾的报告（8）（9）（10）。有些人不能等待干预研究得出明确结果之前可能需要几年的时间。这些包括终末期肾病患者、肾移植受者和心脏移植受者。对他们的高同型半胱氨酸血症立即治疗可能更为谨慎。同型半胱氨酸是一种容易改变的风险因素，对使用水溶性B复合维生素的良性干预策略反应良好（11）（12）（13）。它是通过三步途径从甲硫氨酸衍生而来的（14）。同型半胱氨酸可能具有细胞毒性，并且通过再甲基化回到甲硫氨酸（以完成循环）、在转硫途径中转化为胱硫醚并输出到循环中来维持低细胞内稳态浓度。转硫途径似乎具有高度器官特异性（14），而甜菜碱依赖性再甲基化途径仅在肝脏和肾脏中发现（15）。转硫途径需要吡哆醛...
The etiology and clinical significance of hyperhomocysteinemia are under intense investigation. Although non-genetic (1) and genetic (2)(3)(4) factors influence plasma homocysteine concentrations, the etiology of moderate to intermediate hyperhomocysteinemia (15–50 μmol/L), commonly found in patients with coronary artery disease, cerebrovascular disease, peripheral vascular disease, and in patients with end-stage renal disease, is often unclear. The causes are likely to be multifactorial, involving both acquired and genetic components. There is strong evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular disease (1)(5)(6)(7), but there are conflicting reports as well (8)(9)(10). Some individuals cannot afford to wait the several years it may take before definitive results are available from intervention studies. These include patients with end-stage renal disease, renal transplant recipients, and heart transplant recipients. Immediate treatment of their hyperhomocysteinemia may be more prudent. Homocysteine is an easily modifiable risk factor that responds well to benign intervention strategies using water-soluble B complex vitamins (11)(12)(13). It is derived from methionine in a three-step pathway (14). Homocysteine may be cytotoxic, and low intracellular steady-state concentrations are maintained by remethylation back to methionine (to complete the cycle), conversion to cystathionine in the transsulfuration pathway, and export to the circulation. The transsulfuration pathway appears to be highly organ-specific (14), and the betaine-dependent remethylation pathway is found only in the liver and kidneys (15). The transsulfuration pathway requires pyridoxal …