Independent determinants of soluble form of receptor for advanced glycation end products in elderly hypertensive patients.

Abstract

Advanced glycation end product receptor (RAGE) interaction plays an important role in atherosclerosis. Although exogenously administered soluble form of RAGE (sRAGE) has been shown to suppress the development and progression of atherosclerosis in animals, the kinetics and role of endogenous sRAGE in humans are not fully understood. In this study, to clarify whether endogenous sRAGE could capture and efficiently eliminate RAGE ligands such as circulating AGEs and high-mobility group box-1 (HMGB-1), we investigated the correlation between sRAGE and RAGE ligands and examined independent determinants of serum levels of sRAGE in hypertensive humans. Two-hundred seventy-one consecutive nondiabetic outpatients with essential hypertension (83 male and 188 female; mean age, 76.5 +/- 9.2 years) underwent a complete history, physical examination, and determination of blood chemistries, including serum levels of sRAGE, AGEs, and HMGB-1. Univariate regression analysis showed that serum levels of sRAGE were associated with body mass index (r = -0.313, P < .0001), waist (r = -0.214, P < .0001), alanine aminotransferase (r = -0.172, P = .005), gamma-glutamyltranspeptidase (r = -0.213, P < .0001), 24-hour creatinine clearance (r = -0.348, P < .0001), B-type natriuretic peptide (r = 0.138, P = .027), tumor necrosis factor-alpha (r = 0.138, P = .002), and alcohol intake (r = -0.155, P = .010). By the use of multiple stepwise regression analyses, 24-hour creatinine clearance (P < .0001), gamma-glutamyltranspeptidase (P < .001), body mass index (P = .007), and tumor necrosis factor-alpha (P = .024) remained significant independently. The present study demonstrated for the first time that there was no significant correlation between serum levels of sRAGE and RAGE ligands such as circulating AGEs and HMGB-1 in hypertensive patients. Anthropometric and inflammatory variables and liver and renal function may be the determinants of endogenous sRAGE levels in nondiabetic hypertensive patients.

• Authors: Kazuo Nakamura, Hisashi Adachi, Takanori Matsui, Yayoi Kurita, Masayoshi Takeuchi, Sho-ichi Yamagishi
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 58 Issue 3 Pg. 421-5 (Mar 2009) ISSN: 1532-8600 [Electronic] United States
• PMID: 19217461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycated Hemoglobin A
• Lipids
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Creatinine
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Aged
• Aged, 80 and over
• Alanine Transaminase (blood)
• Aspartate Aminotransferases (blood)
• Blood Pressure
• Creatinine (blood)
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Hyperlipidemias (blood)
• Hypertension (blood)
• Lipids (blood)
• Male
• Patient Selection
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (blood)