Abstract:
Plasma homocysteine (HCY) is an established risk factor for cardiovascular disease CVD and stroke. However, more than two decades of intensive research activities has failed to demonstrate that Hcy lowering through B-vitamin supplementation results in a reduction in CVD risk. Therefore, doubts about a causal involvement of hyperhomocysteinemia (HHcy) and B-vitamin deficiencies in atherosclerosis persist. Existing evidence indicates that HHcy increases oxidative stress, causes endoplasmatic reticulum (ER) stress, alters DNA methylation and, thus, modulates the expression of numerous pathogenic and protective genes. Moreover, Hcy can bind directly to proteins, which can change protein function and impact the intracellular redox state. As most mechanistic evidence is derived from experimental studies with rather artificial settings, the relevance of these results in humans remains a matter of debate. Recently, it has also been proposed that HHcy and B-vitamin deficiencies may promote CVD through accelerated telomere shortening and telomere dysfunction. This review provides a critical overview of the existing literature regarding the role of HHcy and B-vitamin deficiencies in CVD. At present, the CVD risk associated with HHcy and B vitamins is not effectively actionable. Therefore, routine screening for HHcy in CVD patients is of limited value. However, B-vitamin depletion is rather common among the elderly, and in such cases existing deficiencies should be corrected. While Hcy-lowering with high doses of B vitamins has no beneficial effects in secondary CVD prevention, the role of Hcy in primary disease prevention is insufficiently studied. Therefore, more intervention and experimental studies are needed to address existing gaps in knowledge.
摘要:
血浆同型半胱氨酸(HCY)是心血管疾病CVD和中风的既定危险因素。然而,超过20年的深入研究活动未能证明通过补充B族维生素降低Hcy可降低CVD风险.因此,关于高同型半胱氨酸血症(HHcy)和B族维生素缺乏与动脉粥样硬化相关的因果关系的疑虑仍然存在.现有证据表明,HHcy增加氧化应激,引起内质网(ER)应激,改变DNA甲基化,因此,调节许多致病和保护性基因的表达。此外,Hcy可以直接与蛋白质结合,可以改变蛋白质的功能并影响细胞内的氧化还原状态。由于大多数机械证据都来自于人工设置的实验研究,这些结果在人类中的相关性仍然存在争议。最近,也有人提出HHcy和B族维生素缺乏可能通过加速端粒缩短和端粒功能障碍促进CVD。这篇综述提供了有关HHcy和B族维生素缺乏在CVD中的作用的现有文献的重要概述。目前,与HHcy和B族维生素相关的CVD风险不能有效操作.因此,在CVD患者中常规筛查HHcy的价值有限.然而,B族维生素消耗在老年人中相当普遍,在这种情况下,应该纠正现有的缺陷。虽然高剂量B族维生素降低Hcy对二级CVD预防没有有益作用,Hcy在初级疾病预防中的作用研究不足。因此,需要更多的干预和实验研究来解决现有的知识差距。