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[GWICC2013]高同型半胱氨酸血症诱发心血管疾病之机制与治疗策略——王虹教授专访
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作者:王虹 编辑:国际循环网 时间:2013/10/11 13:44:25    加入收藏
 关键字:高同型半胱氨酸血症 叶酸 维生素 蛋白质修饰 

  王虹教授   美国天普大学医学院

  <International Circulation>:  Could you talk about some of the recent progress in epigenetic research regarding vascular injury?

  Prof. Wang Hong: In recent years, epigenetic research into vascular disease has progressed very rapidly. Previously this topic was very popular, a “hot” topic, in the cancer research field but in recent times, we and others in the field have found that epigenetic modifications occur in the atherosclerotic plaque which causes coronary disease very profoundly. We know that throughout the whole plaque, DNA methylation is globally inhibited and that has triggered a lot of study in the gene specific aspect and in different disease settings. So we have some very promising and encouraging discoveries in this field.

  《国际循环》:请您谈一下近年来血管损伤的表观遗传学研究取得了哪些进展?

  王虹教授:近年来,有关血管损伤的表观遗传学研究进展非常迅速。既往表观遗传学是癌症研究领域的热点话题,现在我们发现在导致冠状动脉疾病的动脉粥样硬化斑块中也存在表观遗传修饰现象。我们知道在整个斑块中,DNA的甲基化会被全面抑制。人们开始开展有关各种基因及不同疾病的表观遗传学研究。因此,在这一领域我们有很多令人鼓舞的发现。

  <International Circulation>:  You personally have conducted research into hyperhomocysteinemia. Could you tell us something of the mechanisms of this disease?

  Prof. Wang Hong:  The molecular mechanism underlying homocysteinemia-induced cardiovascular disease (and maybe other disease also because homocysteine has been identified as a potent risk factor for other diseases including Alzheimer’s Disease, other neurodegenerative diseases and other types of cardiovascular disease apart from vascular changes) has also been expanding. The most popular mechanism includes oxidative stress and is the earlier, more classical hypothesis. Recently, we and others have provided strong experimental and clinical evidence supporting hypomethylation which is the topic I have been presenting at this conference. Epigenetic modification is a very important mechanism. This mechanism can explain the disease incidence in the general population. The oxidative stress mechanism probably explains the situation in severe homocysteinemia patients who have a genetic disorder. In the general population, we have other mechanisms provided by the scientific community involving protein modification, protein synthesis and protein editing and I think the field will continue to expand. We will continue to work hard with our colleagues to clarify and characterize different mechanisms and to arrive at a better answer. It is a very rapidly evolving field and is attracting a lot of attention.

  《国际循环》:您作了大量有关高同型半胱氨酸血症的研究。那么高同型半胱氨酸血症引发心血管疾病的主要机制有哪些?

  王虹教授:高同型半胱氨酸血症是包括阿尔茨海默病、神经退行性疾病及其他类型心血管疾病在内的重要危险因素。高同型半胱氨酸血症诱导心血管疾病的分子机制也在不断的增加。其中,最为流行的机制是氧化应激,这是最早的最为经典的假说。最近我们发现大量的实验及临床证据提示“甲基化水平降低也是其重要的机制”。表观遗传学修饰也是非常重要的机制。这一机制,其可以解释疾病在一般人群中的广泛流行。氧化应激机制可能主要适用于有遗传性疾病的严重高同型半胱氨酸血症患者。而对一般人群而言,研究蛋白质修饰、蛋白质合成及蛋白质编辑的科学家发现其还存在蛋白质修饰、蛋白质合成及蛋白质编辑等很多其他机制。我认为,其机制还将不断增加。我们将与我们的同道共同努力来确定和区分各种不同的机制,并得出更好的答案。这一领域的发展极为迅速,备受关注。

  <International Circulation>:  You have mentioned there the work that is going on in the laboratory and its translation into the clinic. Can you give us some insight on how to treat the hyperhomocysteinemic patient?

  Prof. Wang Hong:  The major strategy on the clinical side for treating hyperhomocysteinemia is vitamin therapy. Clinically, the most effective strategy is to provide patients with high doses of folic acid which is a major cofactor for the clearance of homocysteine. In addition to folic acid supplementation, vitamin B6 and vitamin B12 also play a supporting role. In many cases, folic acid in combination with vitamin B12 and vitamin B6 can be very beneficial therapeutically to lower homocysteine and also in reducing the risk for major cardiovascular event recurrence such as stroke which is the condition that has benefitted most from this homocysteine-lowering strategy.

  《国际循环》:您你曾提到实验室工作向临床的转化问题。您认为在临床实践中应如何治疗高同型半胱氨酸血症患者?

  王虹教授:目前高同型半胱氨酸血症主要治疗策略是维生素治疗。临床上,常用的最有效的治疗策略措施是让患者补充高剂量的叶酸。叶酸是清除同型半胱氨酸的重要辅助因素。除叶酸补充剂外,维生素B6及维生素B12也具有很好的疗效。在很多情况下,叶酸与维生素B12及维生素B6联用能在有效降低同型半胱氨酸的同时,降低卒中等主要心血管事件复发风险。患者伴有卒中时最能从叶酸与维生素B12及维生素B6联用治疗中获益。

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