Nenna Antonio, Nappi Francesco, Avtaar Singh Sanjeet Singh, Sutherland Fraser W, Di Domenico Fabio, Chello Massimo, Spadaccio Cristiano
Department of Cardiovascular Sciences, Rome University of Campus Bio Medico, Rome, Italy.
Cardiac Surgery Centre Cardiologique du Nord de Saint-Denis, Paris, France.
Res Cardiovasc Med. 2015 May 23;4(2):e26949. doi: 10.5812/cardiovascmed.4(2)2015.26949. eCollection 2015 May.
Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports.
Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles.
Pharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF.
Despite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.
晚期糖基化终产物（AGEs）是与糖尿病和非糖尿病患者的多种血管及神经并发症相关的信号蛋白。在这些患者的糖尿病管理和外科手术中，AGEs被证明是不良预后的标志物。AGEs的上述作用促使人们研发其效应的药理学抑制剂，从而引发了大量临床前和临床研究。抗AGEs药物的临床试验已逐步开展，本综述旨在总结最相关的报告。
使用PubMed和ClinicalTrials.gov进行证据获取，并对文章进行人工核对。
针对人类的药理学方法包括氨基胍、吡哆胺、苯磷硫胺、血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、他汀类药物、ALT-711（阿格列汀）和噻唑烷二酮类药物。最近有前景的抗AGEs药物是他汀类药物、阿格列汀和噻唑烷二酮类药物。目前临床前研究正在探究AGEs在疾病中的作用以及干扰其效应的新化合物，这些新型抗AGEs药物将在未来几年进行临床评估。具有抗AGEs活性但仍未用于临床的化合物有ALT-946、OPB-9195、替奈西坦、LR-90、TM2002、sRAGE和PEDF。
尽管大多数研究证实了这些药理学方法的疗效，但其他报告产生了相互矛盾的证据；几乎在任何情况下，这些药物的耐受性都良好。目前，AGEs检测在临床实践中仍未发挥精确作用，但其作为疾病标志物的相关性已得到广泛证实；因此，临床医生了解新的心血管危险因素的价值很重要。当前和未来临床试验的结果可能有助于确定AGEs的作用以及抗AGEs治疗在心血管疾病中的益处。
