Role of receptor for advanced glycation end products in cardiogenic shock

Objectives: Activation of the receptor for advanced glycation end products by its ligands promotes inflammatory processes and tissue injury. The available evidence suggests that soluble forms of receptor for advanced glycation end products circulating in the plasma may neutralize the ligand-mediated damage by acting as a decoy. Thus, it is hypothesized that receptor for advanced glycation end products expression might be deleterious, whereas soluble receptor for advanced glycation end products might be beneficial in cardiogenic shock. However, until now, no data exist regarding the role of soluble receptor for advanced glycation end products and receptor for advanced glycation end products in humans with cardiogenic shock complicating myocardial infarction. Design: Prospective observational cohort study. Setting: Intensive critical care unit of a university hospital. Patients: Forty patients with cardiogenic shock complicating acute myocardial infarction, 20 age-matched patients with acute uncomplicated myocardial infarction and, 20 age-matched healthy volunteers. Interventions: None. Measurements and Main Results: Monocytic receptor for advanced glycation end products expression assessed by flow cytometry was significantly increased in cardiogenic shock nonsurvivors (137.02 +/- 7.48 mean fluorescence intensity; n = 13) compared to survivors (67.80 +/- 8.33 mean fluorescence intensity; n = 17; p < .001). Conversely, nonsurvivors had significantly decreased plasma soluble receptor for advanced glycation end products levels (79.87 +/- 10.62 arbitrary units; n = 13; p = .004) compared to survivors (127.65 +/- 10.52 arbitrary units; n = 17) as assessed by Western blotting. Receptor for advanced glycation end products expression and soluble receptor for advanced glycation end products levels were determined as independent predictors for 28-day mortality in cardiogenic shock confirmed by receiver-operator characteristics and multivariate analysis (receptor for advanced glycation end products: area under the curve, 0.943 +/- 0.05; p < .001; soluble receptor for advanced glycation end products: area under the curve, 0.815 +/- 0.08; p < .01). Both receptor for advanced glycation end products >103.6 mean fluorescence intensity or soluble receptor for advanced glycation end products <76.88 arbitrary units independently predicted a 27.87-fold (p < .001) and a 3.97-fold (p = .019) increase in 28-day mortality in cardiogenic shock. Conclusions: Enhanced monocytic receptor for advanced glycation end products expression and decreased plasma soluble receptor for advanced glycation end products levels play a central role in patients with cardiogenic shock associated with proinflammatory and destroying pathways, resulting in an enhanced 28-day mortality-rate. Receptor for advanced glycation end products and soluble receptor for advanced glycation end products may be prognostic biomarkers for survival in cardiogenic shock and might represent a novel therapeutic target in cardiogenic shock. (Crit Care Med 2012; 40: 1513-1522)