title: Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Sciences, Rome University of Campus Bio Medico, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Nenna
authors.affiliation: Cardiac Surgery Centre Cardiologique du Nord de Saint-Denis, Paris, France.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nappi
authors.affiliation: Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Clydebank, Glasgow, UK.
authors.forename: Sanjeet Singh
authors.initials: SS
authors.lastname: Avtaar Singh
authors.affiliation: Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Clydebank, Glasgow, UK.
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Sutherland
authors.affiliation: Department of Biochemical Sciences, La Sapienza University of Rome, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.affiliation: Department of Cardiovascular Sciences, Rome University of Campus Bio Medico, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Chello
authors.affiliation: Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Clydebank, Glasgow, UK.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Spadaccio
keywords: Alagebrium; Benphothiamine; Diabetic Cardiomyopathies; Glycosylation End Products, Advanced; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pimagedine; Pyridoxamine; Thiazolidinediones