Two soluble isoforms of receptors for advanced glycation end products (RAGE) in carotid atherosclerosis: the difference of soluble and endogenous secretory RAGE

Abstract

Background: Advanced glycation end products (AGEs) promote atherosclerosis through binding to their receptor, RAGE. Since soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) may suppress AGEs-RAGE signaling, we examined the usefulness of sRAGE and esRAGE as biomarkers of early-stage atherosclerosis.

Methods: Serum sRAGE and esRAGE levels were measured in 284 subjects with no history of atherothrombotic diseases. The subjects were divided into high-sRAGE and low-sRAGE groups and high-esRAGE and low-esRAGE groups based on respective median values. We investigated the relationships between these parameters and the following factors: number of metabolic components, maximum intima-media thickness of the common carotid artery (IMT Cmax), carotid plaque calcification, and asymptomatic cerebral white matter lesions.

Results: The low-sRAGE and low-esRAGE groups exhibited significantly more components of metabolic syndrome than the high-sRAGE and high-esRAGE groups, respectively. IMT Cmax was significantly higher in the low-sRAGE and low-esRAGE groups. Low-sRAGE levels were significantly associated with carotid plaque calcification. Multiple linear regression analysis identified body mass index (BMI), age, and high-sensitivity C-reactive protein as determinants of sRAGE, whereas only BMI was identified as a determinant of esRAGE.

Conclusions: We demonstrated that sRAGE and esRAGE are associated with atherosclerotic risk factors in early-stage atherosclerosis, suggesting that their levels evolve in correlation with those of metabolic components and inflammation. Interestingly, low-sRAGE and esRAGE levels are associated with high IMT Cmax, but only low-sRAGE levels were associated with carotid plaque calcification. Thus, sRAGE and esRAGE may reflect different aspects of atherosclerosis in its early stage.

Keywords: Soluble receptor for advanced glycation end products; calcification; carotid atherosclerosis; endogenous secretory receptor for advanced glycation end products; intima-media thickness; metabolic component.