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Endogenous secretory RAGE but not soluble RAGE is associated with carotid atherosclerosis in type 1 diabetes patients

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Munehide Matsuhisa

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Hideaki Kaneto

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Taka-Aki Matsuoka

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Ken'Ya Sakamoto

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Tetsuyuki Yasuda

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Yoshimitsu Yamasaki

Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565–0871, Japan.

Advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE) system play an important role in the development of diabetic complications. The soluble form of RAGE (sRAGE) that potentially counteracts AGEs consists of several forms, including endogenous secretory RAGE (esRAGE; a splice variant of RAGE) and cleaved-type soluble RAGE derived from cell-surface RAGE. The aim of this study was to compare sRAGE and esRAGE directly in patients with type 1 diabetes.

The associations of both total sRAGE and esRAGE with markers of glycaemic control and with carotid intimamedia thickness (IMT) as a marker of atherosclerosis were examined in 130 type 1 diabetes patients (aged 23.6±4.9 years) and 22 age-matched non-diabetic subjects.

IMT was inversely correlated with esRAGE (r=–0.254, p=0.0015) but neither with sRAGE nor subtracted soluble RAGE values (that is, circulating total sRAGE values – circulating esRAGE values). Furthermore, a stepwise multivariate regression analysis revealed that esRAGE (F=7.3), but not sRAGE, was a variable that interacted independently of IMT.

It is likely that circulating sRAGE and esRAGE are distinct markers and that circulating esRAGE levels, but not sRAGE levels, are associated with the status of early-stage atherosclerosis.

Key Words: atherosclerosis • esRAGE • RAGE • sRAGE • type 1 diabetes

Diabetes and Vascular Disease Research, Vol. 5, No. 3, 190-197 (2008)
DOI: 10.3132/dvdr.2008.031


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