title: Advanced Glycation End Products and its Soluble Receptors in the Pathogenesis of Thoracic Aortic Aneurysm.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of thoracic aortic aneurysms (TAAs). Cytokines [Interleukin (IL)-Iβ, IL-2, IL-6, and TNF-α)] increase the expression of MMP-2 and -3. Advanced glycation end products (AGEs) interact with cell receptors to increase the release of cytokines. Circulating soluble receptors for AGEs (sRAGE) and endogenous secretory RAGE (esRAGE) compete with membrane bound RAGE for binding with AGEs and reduce the production of cytokines. It is hypothesized that low levels of serum sRAGE and esRAGE and high levels of AGEs, AGEs/sRAGE, and AGEs/esRAGE would increase the levels of cytokines that would increase the levels MMPs, thus contributing to the formation of TAAs.
  
  
  METHODS
  The study population was composed of 17 control subjects and 20 patients with TAA. Blood samples were collected for measurement of serum sRAGE, esRAGE, AGEs, cytokines, and MMPs. AGEs, sRAGE, and esRAGE were measured using ELISA kits, whereas the remaining parameters were measured using the Luminex Multi-Analyte system.
  
  
  RESULTS
  The levels of sRAGE were lower, while the levels of AGEs, AGEs/sRAGE, AGEs/esRAGE, cytokines and MMPs were higher in patients with TAA compared to controls. The levels of sRAGE were inversely correlated with cytokines and MMPs, while AGEs, AGEs/sRAGE and AGEs/esRAGE were positively correlated with cytokines and MMPs. Cytokines were positively correlated with MMPs.
  
  
  CONCLUSIONS
  The data suggest that the AGE-RAGE axis may be involved in the pathogenesis of TAA and that low levels of sRAGE and high levels of AGEs, AGEs/sRAGE, and AGEs/esRAGE are risk factors for TAA.
authors.affiliation: Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Kailash
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA; College of Medicine, Alfaisal University, Ryadh, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Zafar
authors.affiliation: Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shoker
authors.affiliation: Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: Hamdi Ei
authors.initials: HE
authors.lastname: Moselhi
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA.
authors.forename: Maryann
authors.initials: M
authors.lastname: Tranquilli
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA; Department of Surgical Diseases #2, Kazan State Medical University, Kazan, Russia.
authors.forename: Bulat A
authors.initials: BA
authors.lastname: Ziganshin
authors.affiliation: Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Elefteriades
keywords: Advanced glycation end products; Aortic aneurysm; Cytokines; Matrix metalloproteinase; Soluble RAGE; Thoracic aortic aneurysm