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Critical Care  2009 

Advanced glycation endproducts in sepsis and mechanical ventilation: extra or leading man?

DOI: 10.1186/cc7939

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The advanced glycation endproduct (AGE) Nε-carboxy-methyllysine (CML), as recently investigated by Kneyber and colleagues [1], can be formed either from glucose via ketoamine or glyoxal or from lipids by oxidation via glyoxal. This may explain why the pathophysiological role of AGEs is not restricted to diabetes, in which condition they have been primarily studied [2].The enhanced formation of AGEs results in enhanced urinary excretion. In this context, renal-insufficient patients have been associated with CML values several times higher than in healthy controls. Accumulating AGEs can be observed histologically as endothelial depositions in atherosclerotic plaques and tubular cells [3-5]. Their deposition initiates increased NADPH oxidase and nuclear factor κB activity as well as a reduction in endothelial nitric oxide synthase activity [6]. These major effects cause inflammatory changes, extracellular matrix accumulation and endothelial dysfunction. Therefore, AGE accumulation is a potential target for treating inflammatory diseases.The new and interesting idea of Kneyber and colleagues was to investigate the association of CML with myocardial inflammation during sepsis and the clinically relevant state of mechanical ventilation, which by itself is known to induce AGE accumulation in the lungs. This is of relevance as sepsis-induced cardiac dysfunction is a frequent complication associated with increased mortality. Therefore, they focused on a situation where AGE accumulation is increased by systemic inflammation and exacerbated by mechanical ventilation. The association of CML with myocardial inflammation in sepsis and mechanical ventilation is intriguing. Indeed, sepsis enhances CML deposition, which is further aggravated by mechanical ventilation. Thus, the myocardial deposition of AGEs is associated with the disease and the therapeutic approach of mechanical ventilation perpetuates AGE formation.These results raise the question, however, whether the association


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