Kailash Prasad1, Abdullah Sarkar2, Mohammad A Zafar3, Ahmed Shoker4, Hamdi Ei Moselhi4, Maryann Tranquilli3, Bulat A Ziganshin5, John A Elefteriades3. 1. Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 2. Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA; College of Medicine, Alfaisal University, Ryadh, Saudi Arabia. 3. Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA. 4. Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada. 5. Aortic Institute at Yale-New Haven, Yale University School of Medicine, Connecticut, USA; Department of Surgical Diseases #2, Kazan State Medical University, Kazan, Russia.
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.
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: M A Hofmann; S Drury; C Fu; W Qu; A Taguchi; Y Lu; C Avila; N Kambham; A Bierhaus; P Nawroth; M F Neurath; T Slattery; D Beach; J McClary; M Nagashima; J Morser; D Stern; A M Schmidt Journal: Cell Date: 1999-06-25 Impact factor: 41.582
Authors: J Juvonen; H M Surcel; J Satta; A M Teppo; A Bloigu; H Syrjälä; J Airaksinen; M Leinonen; P Saikku; T Juvonen Journal: Arterioscler Thromb Vasc Biol Date: 1997-11 Impact factor: 8.311