Prasad Kailash
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Int J Angiol. 2024 Jul 8;33(4):262-270. doi: 10.1055/s-0044-1788280. eCollection 2024 Dec.
Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B and vitamin B folic acid (vitamin B ). Causes of HHcy include deficiency of vitamins B , B , and B , genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B , and vitamin B lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B , vitamin B , omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.
高同型半胱氨酸血症（HHcy）是动脉粥样硬化的独立危险因素。缺血性中风、心脏病、冠心病和心血管疾病都是长期隐匿性动脉粥样硬化导致的事件。本文论述了同型半胱氨酸（Hcy）的合成、HHcy的病因、HHcy诱导动脉粥样硬化的机制以及HHcy的治疗方法。Hcy的合成与代谢涉及去甲基化、转甲基化和转硫作用，而这些过程需要维生素B6、维生素B12和叶酸（维生素B9）。HHcy的病因包括维生素B6、B12和B9缺乏、基因缺陷、使用无烟烟草、吸烟、饮酒、糖尿病、类风湿关节炎、甲状腺激素水平低、摄入咖啡因、叶酸拮抗剂、降胆固醇药物（烟酸）、叶酸拮抗剂（苯妥英）、长期使用质子泵抑制剂、二甲双胍以及高血压。HHcy诱导的动脉粥样硬化可能通过氧化应激、一氧化氮（NO）可用性降低、单核细胞趋化蛋白-1表达增加、平滑肌细胞增殖、血栓形成增加以及动脉结缔组织诱导来介导。HHcy增加了致动脉粥样硬化生物分子的生成，如核因子-κB、促炎细胞因子（IL-1β、IL-6和IL-8）、细胞黏附分子（细胞间黏附分子-1、血管细胞黏附分子-1和E-选择素）、生长因子（IGF-1和TGF-β）以及单核细胞集落刺激因子，这些都会导致动脉粥样硬化的发展。对动脉粥样硬化发展具有保护作用的NO会被HHcy降低。使用叶酸、维生素B6和维生素B12进行治疗可降低Hcy水平，其中叶酸最为有效。叶酸、维生素B6、维生素B12、ω-3脂肪酸和绿咖啡提取物的膳食来源可降低Hcy。戒除咖啡、酒精和吸烟也可降低血液中的Hcy水平。总之，HHcy通过生成致动脉粥样硬化生物分子诱导动脉粥样硬化，而治疗动脉粥样硬化所致疾病可能需要降低Hcy水平。
