Homocysteine (Hcy) is a non-protein forming amino acid which is the direct metabolic precursor of methionine. Increased concentration of serum Hcy is considered a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature. Serum Hcy is associated with atherosclerosis, hypertension and aneurysms of the aorta in humans, though the precise mechanisms by which Hcy contributes to these conditions remain elusive. Results from clinical trials that successfully lowered serum Hcy without reducing features of vascular disease in cardiovascular patients has cast doubt on whether or not Hcy directly impacts the vasculature. However, studies in animals and in cell culture suggest that Hcy has a vast array of toxic effects on the vasculature, with demonstrated roles in endothelial dysfunction, medial remodeling and adventitial inflammation. It is hypothesized that rather than serum Hcy, tissue-bound Hcy and the incorporation of Hcy into proteins could underlie the toxic effects of Hcy on the vasculature. In this review, we present evidence for Hcy-associated vascular disease in humans, and we critically examine the possible mechanisms by which Hcy specifically impacts the endothelial, medial and adventitial layers of the arterial wall. Deciphering the mechanisms by which Hcy interacts with proteins in the arterial wall will allow for a better understanding of the pathomechanisms of hyperhomocysteinemia and will help to define a better prevention at the appropriate window of life.

中文翻译：

---

同型半胱氨酸诱导的动脉壁内皮层，中间层和外膜层损伤的机制。

同型半胱氨酸（Hcy）是一种非蛋白质形成的氨基酸，是蛋氨酸的直接代谢前体。血清Hcy浓度升高被认为是心血管疾病的危险因素，并且与各种脉管系统疾病特别相关。血清Hcy与人的动脉粥样硬化，高血压和主动脉瘤有关，尽管Hcy促成这些疾病的确切机制仍不清楚。临床试验的结果成功降低了血清Hcy而又未降低心血管患者的血管疾病特征，这使人们对Hcy是否直接影响脉管系统产生了疑问。但是，在动物和细胞培养物中的研究表明，Hcy对血管系统具有多种毒性作用，并已证明在内皮功能异常中具有重要作用，内侧重塑和外膜炎症。假设组织结合的Hcy而不是血清Hcy以及将Hcy掺入蛋白质可能是Hcy对脉管系统的毒性作用的基础。在这篇综述中，我们提供了人类中与Hcy相关的血管疾病的证据，并且我们严格地研究了Hcy特异性影响动脉壁的内皮层，中间层和外膜层的可能机制。阐明Hcy与动脉壁中蛋白质相互作用的机制将使人们更好地了解高同型半胱氨酸血症的发病机理，并有助于在适当的生命周期内确定更好的预防方法。组织结合的Hcy以及将Hcy掺入蛋白质中可能是Hcy对脉管系统的毒性作用的基础。在这篇综述中，我们提供了人类中与Hcy相关的血管疾病的证据，并且我们严格地研究了Hcy特异性影响动脉壁的内皮层，中间层和外膜层的可能机制。阐明Hcy与动脉壁中蛋白质相互作用的机制将使人们更好地了解高同型半胱氨酸血症的发病机制，并有助于在适当的生命周期内确定更好的预防方法。组织结合的Hcy以及将Hcy掺入蛋白质中可能是Hcy对脉管系统的毒性作用的基础。在这篇综述中，我们提供了人类中与Hcy相关的血管疾病的证据，并且我们严格地研究了Hcy特异性影响动脉壁的内皮层，中间层和外膜层的可能机制。阐明Hcy与动脉壁中蛋白质相互作用的机制将使人们更好地了解高同型半胱氨酸血症的发病机理，并有助于在适当的生命周期内确定更好的预防方法。动脉壁的内侧和外膜层。阐明Hcy与动脉壁中蛋白质相互作用的机制将使人们更好地了解高同型半胱氨酸血症的发病机理，并有助于在适当的生命周期内确定更好的预防方法。动脉壁的内侧和外膜层。阐明Hcy与动脉壁中蛋白质相互作用的机制将使人们更好地了解高同型半胱氨酸血症的发病机理，并有助于在适当的生命周期内确定更好的预防方法。