Vizzardi Enrico, Bonadei Ivano, Zanini Gregoriana, Frattini Silvia, Fiorina Claudia, Raddino Riccardo, Dei Cas Livio
Department of Cardiology, University of Brescia, Brescia, Italy.
Recent Pat Cardiovasc Drug Discov. 2009 Jan;4(1):15-21. doi: 10.2174/157489009787259991.
An elevated plasma level of homocysteine (HCY) is associated with increased risk of thrombotic and atherosclerotic vascular disease. Several studies and recent patents have demonstrated that hyper-homocysteinemia (HHCY) is an independent risk factor for vascular disease. An elevated homocysteine level has been also reported to be a risk factor for the development of congestive heart failure (CHF) in individuals free of myocardial infarction. Animal studies showed that experimental HHCY induces systolic and diastolic dysfunction, as well as an increased BNP expression. Moreover, hyperhomocysteinemic animals exhibit an adverse cardiac remodeling characterized by accumulation of interstitial and perivascular collagen. The mechanisms leading from an elevated HCY level to reduced pump function and adverse cardiac remodeling are a matter of speculation. Existing data indicate that direct effects of HCY on the myocardium, as well as nitric oxide independent vascular effects, are involved. Preliminary data from small intervention trials have initiated the speculation that HCY lowering therapy by micronutrients may improve clinical as well as laboratory markers of CHF. In conclusion, HHCY might be a potential etiological factor in CHF. Future studies need to explore the exact pathomechanisms of HHCY in CHF. Moreover, larger intervention trials are needed to clarify whether modification of plasma HCY by B-vitamin supplementation improves the clinical outcome in CHF patients.
血浆同型半胱氨酸（HCY）水平升高与血栓形成和动脉粥样硬化性血管疾病风险增加相关。多项研究及近期专利表明，高同型半胱氨酸血症（HHCY）是血管疾病的独立危险因素。据报道，在无心肌梗死的个体中，同型半胱氨酸水平升高也是发生充血性心力衰竭（CHF）的危险因素。动物研究显示，实验性HHCY可导致收缩和舒张功能障碍，以及脑钠肽（BNP）表达增加。此外，高同型半胱氨酸血症动物表现出以间质和血管周围胶原积聚为特征的不良心脏重塑。从HCY水平升高到泵功能降低及不良心脏重塑的机制尚在推测中。现有数据表明，HCY对心肌的直接作用以及不依赖一氧化氮的血管作用均有涉及。小型干预试验的初步数据引发了这样的推测，即通过微量营养素降低HCY的治疗可能改善CHF的临床及实验室指标。总之，HHCY可能是CHF的一个潜在病因。未来的研究需要探索HHCY在CHF中的确切发病机制。此外，需要更大规模的干预试验来阐明补充B族维生素对血浆HCY的调节是否能改善CHF患者的临床结局。
