Tang RiBo, Ma ChangSheng, Dong JianZeng, Liu XingPeng, Liu Xiaohui
Department of Cardiology, Beijing AnZhen Hospital, Capital University of Medical Sciences, Chaoyang District, Beijing 100029, China.
Med Hypotheses. 2006;67(2):371-4. doi: 10.1016/j.mehy.2006.01.038.
Adenosine deaminase (ADA) is an enzyme which catalyzes adenosine to inosine. Patients who inherently lack the enzyme have defects in both humoral and cellular immunity. ADA plays an important role in many immunity mediate diseases, such as asthma, Graves' disease and tuberculosis. Coronary artery disease (CAD) has been considered as an inflammatory and immunizing disease recently. However, there are few reports about the effect of ADA in cardiovascular fields. In fact, ADA may play a key role in the immunity, inflammation and other aspects of CAD. This hypothesis is potentially based on three aspects of evolution. First, ADA inhibitors attenuate the elevation of proinflammatory factors, which shows ADA mediate in the inflammation response. ADA also has effect on the activation of complement system by the deamination of adenosine. Thus, ADA has a role in CAD by affecting inflammation process. Second, many effects produced by ADA are caused by the metabolism of adenosine. It is known that adenosine can inhibit the invasion of the neutrophil so as to attenuate the ischemic/reperfusion injury . Adenosine can increase coronary artery blood flow during active stress and hypoxia to balance the oxygen supply and demand. Adenosine can also account for the majority of basal vascular endothelial growth factor (VEGF) mRNA and protein expression in cultured myocardial vascular smooth muscle cells under normoxic conditions to stimulate the angiogenesis. If adenosine is rapidly metabolized by the high level of ADA, the advantages of adenosine will lost. Finally, adenosine is catalyzed to inosine, which can produce superoxide radicals and exaggerate the ischemic/reperfusion injury. In conclusion ADA can have a crucial role in CAD, if design and development of therapeutic strategies against ADA is guaranteed, an innovational therapeutic approach to CAD can be realized.
腺苷脱氨酶(ADA)是一种催化腺苷转化为肌苷的酶。天生缺乏该酶的患者在体液免疫和细胞免疫方面均有缺陷。ADA在许多免疫介导的疾病中发挥重要作用,如哮喘、格雷夫斯病和结核病。冠状动脉疾病(CAD)最近被认为是一种炎症和免疫性疾病。然而,关于ADA在心血管领域作用的报道很少。事实上,ADA可能在CAD的免疫、炎症等方面发挥关键作用。这一假设可能基于三个进化方面。首先,ADA抑制剂可减轻促炎因子的升高,这表明ADA参与炎症反应。ADA还通过腺苷脱氨作用对补体系统的激活产生影响。因此,ADA通过影响炎症过程在CAD中发挥作用。其次,ADA产生的许多效应是由腺苷的代谢引起的。众所周知,腺苷可抑制中性粒细胞的侵袭,从而减轻缺血/再灌注损伤。腺苷可在运动应激和缺氧期间增加冠状动脉血流量,以平衡氧供需。腺苷还可在常氧条件下占培养的心肌血管平滑肌细胞中基础血管内皮生长因子(VEGF)mRNA和蛋白表达的大部分,以刺激血管生成。如果腺苷被高水平的ADA快速代谢,腺苷的优势将丧失。最后,腺苷被催化为肌苷,可产生超氧自由基并加剧缺血/再灌注损伤。总之,ADA在CAD中可能起关键作用,如果保证针对ADA的治疗策略的设计和开发,就可以实现一种创新的CAD治疗方法。