Two Soluble Isoforms of Receptors for Advanced Glycation End Products (RAGE) in Carotid Atherosclerosis: The Difference of Soluble and Endogenous Secretory RAGE

• Published in: Journal of stroke and cerebrovascular diseases 2014-11, Vol.23 (10), p.2540-2546
• Main Authors: Moriya, Saori, MD, Yamazaki, Masako, MD, PhD, Murakami, Hirohiko, MD, PhD, Maruyama, Kenji, MD, PhD, Uchiyama, Shinichiro, MD, PhD
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Biomarkers - blood; Body Mass Index; C-Reactive Protein - analysis; calcification; Cardiovascular; Carotid Artery Diseases - blood; Carotid Artery Diseases - pathology; Carotid Artery, Common - pathology; carotid atherosclerosis; Carotid Intima-Media Thickness; Carotid Stenosis - blood; Carotid Stenosis - pathology; endogenous secretory receptor for advanced glycation end products; Female; Glycation End Products, Advanced - blood; Glycation End Products, Advanced - classification; Humans; intima-media thickness; Linear Models; Male; metabolic component; Metabolic Syndrome - blood; Metabolic Syndrome - pathology; Middle Aged; Neurology; Protein Isoforms; Risk Factors; Soluble receptor for advanced glycation end products; Vascular Calcification - blood; Vascular Calcification - pathology
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2014.05.037

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.